Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Identifieur interne : 000585 ( Istex/Curation ); précédent : 000584; suivant : 000586Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Auteurs : Yi Li ; Sofia Oliveira ; Puting Xu ; Eden Martin ; Judith Stenger ; Clemens Scherzer ; Michael Hauser ; William Scott ; Gary Small ; Martha Nance ; Ray Watts ; Jean Hubble ; William Koller ; Rajesh Pahwa ; Mathew Stern ; Bradley Hiner ; Joseph Jankovic ; Christopher Goetz ; Frank Mastaglia ; Lefkos Middleton ; Allen Roses ; Ann Saunders ; Donald Schmechel ; Steven Gullans ; Jonathan Haines [États-Unis] ; John Gilbert ; Jeffery Vance ; Margaret PericakSource :
- 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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Yi Li<affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66045, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia 6009, Australia,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><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><wicri:noCountry code="subField">USA and</wicri:noCountry></affiliation><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation>Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title 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" last="Li">Yi Li</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith" last="Stenger">Judith Stenger</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens" last="Scherzer">Clemens Scherzer</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael" last="Hauser">Michael Hauser</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary" last="Small">Gary Small</name><affiliation><mods:affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><affiliation><mods:affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name><affiliation><mods:affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean" last="Hubble">Jean Hubble</name><affiliation><mods:affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name><affiliation><mods:affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew" last="Stern">Mathew Stern</name><affiliation><mods:affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley" last="Hiner">Bradley Hiner</name><affiliation><mods:affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name><affiliation><mods:affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen" last="Roses">Allen Roses</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann" last="Saunders">Ann Saunders</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald 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><wicri:noCountry code="subField">USA and</wicri:noCountry></affiliation></author><author><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven" last="Gullans">Steven Gullans</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan Haines</name><affiliation wicri:level="1"><mods:affiliation>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232</wicri:regionArea></affiliation></author><author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John" last="Gilbert">John Gilbert</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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/Istex/Corpus">000585</idno><idno type="wicri:Area/Istex/Curation">000585</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" last="Li">Yi Li</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith" last="Stenger">Judith Stenger</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens" last="Scherzer">Clemens Scherzer</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael" last="Hauser">Michael Hauser</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary" last="Small">Gary Small</name><affiliation><mods:affiliation>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California, Los Angeles, CA 90024, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><affiliation><mods:affiliation>Struthers Parkinson Center, Golden Valley, MN 55426, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name><affiliation><mods:affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean" last="Hubble">Jean Hubble</name><affiliation><mods:affiliation>Department of Neurology, Ohio State University, Columbus, OH 43210, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name><affiliation><mods:affiliation>Department of Neurology, University of Miami School of Medicine, Miami, FL 33124, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew" last="Stern">Mathew Stern</name><affiliation><mods:affiliation>Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley" last="Hiner">Bradley Hiner</name><affiliation><mods:affiliation>Department of Neurology, Marshfield Clinic, Marshfield, WI 54449, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian–St Luke's Hospital, Chicago, IL 60612, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name><affiliation><mods:affiliation>GlaxoSmithKline Research and Development, Greenford, Middlesex UB6 0HE, UK,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen" last="Roses">Allen Roses</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann" last="Saunders">Ann Saunders</name><affiliation><mods:affiliation>GlaxoSmithKline Genetics Research Directorate, Research Triangle Park, NC, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald 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><wicri:noCountry code="subField">USA and</wicri:noCountry></affiliation></author><author><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven" last="Gullans">Steven Gullans</name><affiliation><mods:affiliation>Harvard University Medical School, Boston, MA 02115, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan Haines</name><affiliation wicri:level="1"><mods:affiliation>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232</wicri:regionArea></affiliation></author><author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John" last="Gilbert">John Gilbert</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name><affiliation><mods:affiliation>Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA,</mods:affiliation><wicri:noCountry code="subField"></wicri:noCountry></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></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></record>Pour manipuler ce document sous Unix (Dilib)
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