Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Identifieur interne : 000A17 ( Main/Corpus ); précédent : 000A16; suivant : 000A18Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Auteurs : Yi-Ju Li ; Sofia A. Oliveira ; Puting Xu ; Eden R. Martin ; Judith E. Stenger ; Clemens R. Scherzer ; Michael A. Hauser ; William K. Scott ; Gary W. Small ; Martha A. Nance ; Ray L. Watts ; Jean P. Hubble ; William C. Koller ; Rajesh Pahwa ; Mathew B. Stern ; Bradley C. Hiner ; Joseph Jankovic ; Christopher G. Goetz ; Frank Mastaglia ; Lefkos T. Middleton ; Allen D. Roses ; Ann M. Saunders ; Donald E. Schmechel ; Steven R. Gullans ; Jonathan L. Haines ; John R. Gilbert ; Jeffery M. Vance ; Margaret A. Pericak-VanceSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2003-12-15.
Abstract
We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.
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DOI: 10.1093/hmg/ddg357
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Scott</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary W." last="Small">Gary W. Small</name><affiliation><mods:affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</mods:affiliation></affiliation></author><author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha A." last="Nance">Martha A. Nance</name><affiliation><mods:affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</mods:affiliation></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L." last="Watts">Ray L. Watts</name><affiliation><mods:affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</mods:affiliation></affiliation></author><author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean P." last="Hubble">Jean P. Hubble</name><affiliation><mods:affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</mods:affiliation></affiliation></author><author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William C." last="Koller">William C. Koller</name><affiliation><mods:affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</mods:affiliation></affiliation></author><author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</mods:affiliation></affiliation></author><author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew B." last="Stern">Mathew B. Stern</name><affiliation><mods:affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</mods:affiliation></affiliation></author><author><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley C." last="Hiner">Bradley C. Hiner</name><affiliation><mods:affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</mods:affiliation></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</mods:affiliation></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G." last="Goetz">Christopher G. Goetz</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</mods:affiliation></affiliation></author><author><name sortKey="Mastaglia, Frank" sort="Mastaglia, Frank" uniqKey="Mastaglia F" first="Frank" last="Mastaglia">Frank Mastaglia</name><affiliation><mods:affiliation>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</mods:affiliation></affiliation></author><author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos T." last="Middleton">Lefkos T. Middleton</name><affiliation><mods:affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</mods:affiliation></affiliation></author><author><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen D." last="Roses">Allen D. Roses</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation></affiliation></author><author><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann M." last="Saunders">Ann M. Saunders</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation></affiliation></author><author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald E." last="Schmechel">Donald E. Schmechel</name><affiliation><mods:affiliation>Department of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA and</mods:affiliation></affiliation></author><author><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven R." last="Gullans">Steven R. Gullans</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L." last="Haines">Jonathan L. Haines</name><affiliation><mods:affiliation>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</mods:affiliation></affiliation></author><author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John R." last="Gilbert">John R. Gilbert</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret A." last="Pericak-Vance">Margaret A. Pericak-Vance</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:309BE1DA604A9377F0D3B3DAE63A38B7592B7A24</idno><date when="2003" year="2003">2003</date><idno type="doi">10.1093/hmg/ddg357</idno><idno type="url">https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000A17</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title><author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia A." last="Oliveira">Sofia A. Oliveira</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Xu, Puting" sort="Xu, Puting" uniqKey="Xu P" first="Puting" last="Xu">Puting Xu</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden R." last="Martin">Eden R. Martin</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith E." last="Stenger">Judith E. Stenger</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. Scott</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary W." last="Small">Gary W. Small</name><affiliation><mods:affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</mods:affiliation></affiliation></author><author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha A." last="Nance">Martha A. Nance</name><affiliation><mods:affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</mods:affiliation></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L." last="Watts">Ray L. Watts</name><affiliation><mods:affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</mods:affiliation></affiliation></author><author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean P." last="Hubble">Jean P. Hubble</name><affiliation><mods:affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</mods:affiliation></affiliation></author><author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William C." last="Koller">William C. Koller</name><affiliation><mods:affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</mods:affiliation></affiliation></author><author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</mods:affiliation></affiliation></author><author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew B." last="Stern">Mathew B. Stern</name><affiliation><mods:affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</mods:affiliation></affiliation></author><author><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley C." last="Hiner">Bradley C. Hiner</name><affiliation><mods:affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</mods:affiliation></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</mods:affiliation></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G." last="Goetz">Christopher G. Goetz</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</mods:affiliation></affiliation></author><author><name sortKey="Mastaglia, Frank" sort="Mastaglia, Frank" uniqKey="Mastaglia F" first="Frank" last="Mastaglia">Frank Mastaglia</name><affiliation><mods:affiliation>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</mods:affiliation></affiliation></author><author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos T." last="Middleton">Lefkos T. Middleton</name><affiliation><mods:affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</mods:affiliation></affiliation></author><author><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen D." last="Roses">Allen D. Roses</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation></affiliation></author><author><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann M." last="Saunders">Ann M. Saunders</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation></affiliation></author><author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald E." last="Schmechel">Donald E. Schmechel</name><affiliation><mods:affiliation>Department of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA and</mods:affiliation></affiliation></author><author><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven R." last="Gullans">Steven R. Gullans</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L." last="Haines">Jonathan L. Haines</name><affiliation><mods:affiliation>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</mods:affiliation></affiliation></author><author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John R." last="Gilbert">John R. Gilbert</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret A." last="Pericak-Vance">Margaret A. Pericak-Vance</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. Genet.</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-12-15">2003-12-15</date><biblScope unit="volume">12</biblScope><biblScope unit="issue">24</biblScope><biblScope unit="page" from="3259">3259</biblScope><biblScope unit="page" to="3267">3267</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">309BE1DA604A9377F0D3B3DAE63A38B7592B7A24</idno><idno type="DOI">10.1093/hmg/ddg357</idno><idno type="local">ddg357</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Yi-Ju Li</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Sofia A. Oliveira</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Puting Xu</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Eden R. Martin</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Judith E. Stenger</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Clemens R. Scherzer</name><affiliations><json:string>Harvard University Medical School, Boston, MA 02115, USA,</json:string></affiliations></json:item><json:item><name>Michael A. Hauser</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>William K. Scott</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Gary W. Small</name><affiliations><json:string>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</json:string></affiliations></json:item><json:item><name>Martha A. Nance</name><affiliations><json:string>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</json:string></affiliations></json:item><json:item><name>Ray L. Watts</name><affiliations><json:string>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</json:string></affiliations></json:item><json:item><name>Jean P. Hubble</name><affiliations><json:string>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</json:string></affiliations></json:item><json:item><name>William C. Koller</name><affiliations><json:string>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</json:string></affiliations></json:item><json:item><name>Rajesh Pahwa</name><affiliations><json:string>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</json:string></affiliations></json:item><json:item><name>Mathew B. Stern</name><affiliations><json:string>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</json:string></affiliations></json:item><json:item><name>Bradley C. Hiner</name><affiliations><json:string>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</json:string></affiliations></json:item><json:item><name>Joseph Jankovic</name><affiliations><json:string>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</json:string></affiliations></json:item><json:item><name>Christopher G. Goetz</name><affiliations><json:string>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</json:string></affiliations></json:item><json:item><name>Frank Mastaglia</name><affiliations><json:string>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</json:string></affiliations></json:item><json:item><name>Lefkos T. Middleton</name><affiliations><json:string>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</json:string></affiliations></json:item><json:item><name>Allen D. Roses</name><affiliations><json:string>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</json:string></affiliations></json:item><json:item><name>Ann M. Saunders</name><affiliations><json:string>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</json:string></affiliations></json:item><json:item><name>Donald E. Schmechel</name><affiliations><json:string>Department of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA and</json:string></affiliations></json:item><json:item><name>Steven R. Gullans</name><affiliations><json:string>Harvard University Medical School, Boston, MA 02115, USA,</json:string></affiliations></json:item><json:item><name>Jonathan L. Haines</name><affiliations><json:string>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</json:string></affiliations></json:item><json:item><name>John R. Gilbert</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Jeffery M. Vance</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item><json:item><name>Margaret A. Pericak-Vance</name><affiliations><json:string>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Article</value></json:item></subject><language><json:string>eng</json:string></language><abstract>We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</abstract><qualityIndicators><score>7.676</score><pdfVersion>1.2</pdfVersion><pdfPageSize>609.675 x 795.005 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>1</keywordCount><abstractCharCount>1514</abstractCharCount><pdfWordCount>5307</pdfWordCount><pdfCharCount>34466</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>223</abstractWordCount></qualityIndicators><title>Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title><genre><json:string>research-article</json:string></genre><host><volume>12</volume><pages><last>3267</last><first>3259</first></pages><issn><json:string>0964-6906</json:string></issn><issue>24</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2083</json:string></eissn><title>Human Molecular Genetics</title></host><categories><wos><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string><json:string>GENETICS & HEREDITY</json:string></wos></categories><publicationDate>2003</publicationDate><copyrightDate>2003</copyrightDate><doi><json:string>10.1093/hmg/ddg357</json:string></doi><id>309BE1DA604A9377F0D3B3DAE63A38B7592B7A24</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2003</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title><author><persName><forename type="first">Yi-Ju</forename><surname>Li</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Sofia A.</forename><surname>Oliveira</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Puting</forename><surname>Xu</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Eden R.</forename><surname>Martin</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Judith E.</forename><surname>Stenger</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Clemens R.</forename><surname>Scherzer</surname></persName><affiliation>Harvard University Medical School, Boston, MA 02115, USA,</affiliation></author><author><persName><forename type="first">Michael A.</forename><surname>Hauser</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">William K.</forename><surname>Scott</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Gary W.</forename><surname>Small</surname></persName><affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</affiliation></author><author><persName><forename type="first">Martha A.</forename><surname>Nance</surname></persName><affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</affiliation></author><author><persName><forename type="first">Ray L.</forename><surname>Watts</surname></persName><affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</affiliation></author><author><persName><forename type="first">Jean P.</forename><surname>Hubble</surname></persName><affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</affiliation></author><author><persName><forename type="first">William C.</forename><surname>Koller</surname></persName><affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</affiliation></author><author><persName><forename type="first">Rajesh</forename><surname>Pahwa</surname></persName><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</affiliation></author><author><persName><forename type="first">Mathew B.</forename><surname>Stern</surname></persName><affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</affiliation></author><author><persName><forename type="first">Bradley C.</forename><surname>Hiner</surname></persName><affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</affiliation></author><author><persName><forename type="first">Joseph</forename><surname>Jankovic</surname></persName><affiliation>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</affiliation></author><author><persName><forename type="first">Christopher G.</forename><surname>Goetz</surname></persName><affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</affiliation></author><author><persName><forename type="first">Frank</forename><surname>Mastaglia</surname></persName><affiliation>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</affiliation></author><author><persName><forename type="first">Lefkos T.</forename><surname>Middleton</surname></persName><affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</affiliation></author><author><persName><forename type="first">Allen D.</forename><surname>Roses</surname></persName><affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</affiliation></author><author><persName><forename type="first">Ann M.</forename><surname>Saunders</surname></persName><affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</affiliation></author><author><persName><forename type="first">Donald E.</forename><surname>Schmechel</surname></persName><affiliation>Department of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA and</affiliation></author><author><persName><forename type="first">Steven R.</forename><surname>Gullans</surname></persName><affiliation>Harvard University Medical School, Boston, MA 02115, USA,</affiliation></author><author><persName><forename type="first">Jonathan L.</forename><surname>Haines</surname></persName><affiliation>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</affiliation></author><author><persName><forename type="first">John R.</forename><surname>Gilbert</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Jeffery M.</forename><surname>Vance</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author><author><persName><forename type="first">Margaret A.</forename><surname>Pericak-Vance</surname></persName><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation></author></analytic><monogr><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. Genet.</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-12-15"></date><biblScope unit="volume">12</biblScope><biblScope unit="issue">24</biblScope><biblScope unit="page" from="3259">3259</biblScope><biblScope unit="page" to="3267">3267</biblScope></imprint></monogr><idno type="istex">309BE1DA604A9377F0D3B3DAE63A38B7592B7A24</idno><idno type="DOI">10.1093/hmg/ddg357</idno><idno type="local">ddg357</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2003</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</p></abstract></profileDesc><revisionDesc><change when="2003-12-15">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-15">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">hmg</journal-id><journal-id journal-id-type="nlm-ta">Hum Mol Genet</journal-id><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><abbrev-journal-title abbrev-type="publisher">Hum. Mol. Genet.</abbrev-journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="other">ddg357</article-id><article-id pub-id-type="doi">10.1093/hmg/ddg357</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Glutathione <italic>S</italic>-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yi-Ju</given-names></name><xref rid="AF1">1</xref><xref rid="FN1">*</xref><xref rid="FN2">†</xref></contrib><contrib contrib-type="author"><name><surname>Oliveira</surname><given-names>Sofia A.</given-names></name><xref rid="AF1">1</xref><xref rid="FN2">†</xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Puting</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Eden R.</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Stenger</surname><given-names>Judith E.</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Scherzer</surname><given-names>Clemens R.</given-names></name><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Hauser</surname><given-names>Michael A.</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>William K.</given-names></name><xref rid="AF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Small</surname><given-names>Gary W.</given-names></name><xref rid="AF3">3</xref></contrib><contrib contrib-type="author"><name><surname>Nance</surname><given-names>Martha A.</given-names></name><xref rid="AF4">4</xref></contrib><contrib contrib-type="author"><name><surname>Watts</surname><given-names>Ray L.</given-names></name><xref rid="AF5">5</xref></contrib><contrib contrib-type="author"><name><surname>Hubble</surname><given-names>Jean P.</given-names></name><xref rid="AF6">6</xref></contrib><contrib contrib-type="author"><name><surname>Koller</surname><given-names>William C.</given-names></name><xref rid="AF7">7</xref></contrib><contrib contrib-type="author"><name><surname>Pahwa</surname><given-names>Rajesh</given-names></name><xref rid="AF8">8</xref></contrib><contrib contrib-type="author"><name><surname>Stern</surname><given-names>Mathew B.</given-names></name><xref rid="AF9">9</xref></contrib><contrib contrib-type="author"><name><surname>Hiner</surname><given-names>Bradley C.</given-names></name><xref rid="AF10">10</xref></contrib><contrib contrib-type="author"><name><surname>Jankovic</surname><given-names>Joseph</given-names></name><xref rid="AF11">11</xref></contrib><contrib contrib-type="author"><name><surname>Goetz</surname><given-names>Christopher G.</given-names></name><xref rid="AF12">12</xref></contrib><contrib contrib-type="author"><name><surname>Mastaglia</surname><given-names>Frank</given-names></name><xref rid="AF13">13</xref></contrib><contrib contrib-type="author"><name><surname>Middleton</surname><given-names>Lefkos T.</given-names></name><xref rid="AF14">14</xref></contrib><contrib contrib-type="author"><name><surname>Roses</surname><given-names>Allen D.</given-names></name><xref rid="AF15">15</xref></contrib><contrib contrib-type="author"><name><surname>Saunders</surname><given-names>Ann M.</given-names></name><xref rid="AF15">15</xref></contrib><contrib contrib-type="author"><name><surname>Schmechel</surname><given-names>Donald E.</given-names></name><xref rid="AF16">16</xref></contrib><contrib contrib-type="author"><name><surname>Gullans</surname><given-names>Steven R.</given-names></name><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Haines</surname><given-names>Jonathan L.</given-names></name><xref rid="AF17">17</xref><xref rid="FN3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Gilbert</surname><given-names>John R.</given-names></name><xref rid="AF1">1</xref><xref rid="FN3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Vance</surname><given-names>Jeffery M.</given-names></name><xref rid="AF1">1</xref><xref rid="FN3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Pericak-Vance</surname><given-names>Margaret A.</given-names></name><xref rid="AF1">1</xref><xref rid="FN3">‡</xref></contrib><aff id="AF1"><sup>1</sup>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</aff><aff id="AF2"><sup>2</sup>Harvard University Medical School, Boston, MA 02115, USA,</aff><aff id="AF3"><sup>3</sup>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</aff><aff id="AF4"><sup>4</sup>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</aff><aff id="AF5"><sup>5</sup>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</aff><aff id="AF6"><sup>6</sup>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</aff><aff id="AF7"><sup>7</sup>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</aff><aff id="AF8"><sup>8</sup>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</aff><aff id="AF9"><sup>9</sup>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</aff><aff id="AF10"><sup>10</sup>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</aff><aff id="AF11"><sup>11</sup>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</aff><aff id="AF12"><sup>12</sup>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</aff><aff id="AF13"><sup>13</sup>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</aff><aff id="AF14"><sup>14</sup>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</aff><aff id="AF15"><sup>15</sup>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</aff><aff id="AF16"><sup>16</sup>Department of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA and</aff><aff id="AF17"><sup>17</sup>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</aff></contrib-group><pub-date pub-type="ppub"><day>15</day><month>12</month><year>2003</year></pub-date><volume>12</volume><issue>24</issue><fpage>3259</fpage><lpage>3267</lpage><history><date date-type="accepted"><day>29</day><month>09</month><year>2003</year></date><date date-type="received"><day>7</day><month>07</month><year>2003</year></date><date date-type="rev-recd"><day>22</day><month>09</month><year>2003</year></date></history><permissions><copyright-year>2003</copyright-year></permissions><abstract xml:lang="en"><p>We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione <italic>S</italic>-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (<italic>P</italic>=0.007) and a second transcribed member of the GST omega class, GSTO2 (<italic>P</italic>=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</p></abstract><custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name><meta-value>3259</meta-value></custom-meta><custom-meta><meta-name>hwp-legacy-dochead</meta-name><meta-value>Article</meta-value></custom-meta></custom-meta-wrap></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title></titleInfo><name type="personal"><namePart type="given">Yi-Ju</namePart><namePart type="family">Li</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sofia A.</namePart><namePart type="family">Oliveira</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Puting</namePart><namePart type="family">Xu</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eden R.</namePart><namePart type="family">Martin</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Judith E.</namePart><namePart type="family">Stenger</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Clemens R.</namePart><namePart type="family">Scherzer</namePart><affiliation>Harvard University Medical School, Boston, MA 02115, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael A.</namePart><namePart type="family">Hauser</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William K.</namePart><namePart type="family">Scott</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gary W.</namePart><namePart type="family">Small</namePart><affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martha A.</namePart><namePart type="family">Nance</namePart><affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ray L.</namePart><namePart type="family">Watts</namePart><affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean P.</namePart><namePart type="family">Hubble</namePart><affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William C.</namePart><namePart type="family">Koller</namePart><affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rajesh</namePart><namePart type="family">Pahwa</namePart><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mathew B.</namePart><namePart type="family">Stern</namePart><affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bradley C.</namePart><namePart type="family">Hiner</namePart><affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joseph</namePart><namePart type="family">Jankovic</namePart><affiliation>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christopher G.</namePart><namePart type="family">Goetz</namePart><affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Frank</namePart><namePart type="family">Mastaglia</namePart><affiliation>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lefkos T.</namePart><namePart type="family">Middleton</namePart><affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Allen D.</namePart><namePart type="family">Roses</namePart><affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ann M.</namePart><namePart type="family">Saunders</namePart><affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald E.</namePart><namePart type="family">Schmechel</namePart><affiliation>Department of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Steven R.</namePart><namePart type="family">Gullans</namePart><affiliation>Harvard University Medical School, Boston, MA 02115, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jonathan L.</namePart><namePart type="family">Haines</namePart><affiliation>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John R.</namePart><namePart type="family">Gilbert</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jeffery M.</namePart><namePart type="family">Vance</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Margaret A.</namePart><namePart type="family">Pericak-Vance</namePart><affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2003-12-15</dateIssued><copyrightDate encoding="w3cdtf">2003</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mol. Genet.</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><identifier type="PublisherID-nlm-ta">Hum Mol Genet</identifier><part><date>2003</date><detail type="volume"><caption>vol.</caption><number>12</number></detail><detail type="issue"><caption>no.</caption><number>24</number></detail><extent unit="pages"><start>3259</start><end>3267</end></extent></part></relatedItem><identifier type="istex">309BE1DA604A9377F0D3B3DAE63A38B7592B7A24</identifier><identifier type="DOI">10.1093/hmg/ddg357</identifier><identifier type="local">ddg357</identifier><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/309BE1DA604A9377F0D3B3DAE63A38B7592B7A24/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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