Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Identifieur interne : 001760 ( Main/Exploration ); précédent : 001759; suivant : 001761Glutathione 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 [États-Unis] ; Christopher G. Goetz ; Frank Mastaglia ; Lefkos T. Middleton ; Allen D. Roses ; Ann M. Saunders ; Donald E. Schmechel ; Steven R. Gullans ; Jonathan L. Haines [États-Unis] ; 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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Haines</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></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><wicri:noCountry code="subField"></wicri:noCountry></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><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 A." last="Pericak-Vance">Margaret A. Pericak-Vance</name><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><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><affiliations><list><country><li>États-Unis</li></country><region><li>Tennessee</li><li>Texas</li></region><settlement><li>Houston</li></settlement><orgName><li>Baylor College of Medicine</li></orgName></list><tree><noCountry><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John R." last="Gilbert">John R. Gilbert</name><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G." last="Goetz">Christopher G. Goetz</name><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven R." last="Gullans">Steven R. Gullans</name><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley C." last="Hiner">Bradley C. Hiner</name><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean P." last="Hubble">Jean P. Hubble</name><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William C." last="Koller">William C. Koller</name><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden R." last="Martin">Eden R. Martin</name><name sortKey="Mastaglia, Frank" sort="Mastaglia, Frank" uniqKey="Mastaglia F" first="Frank" last="Mastaglia">Frank Mastaglia</name><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos T." last="Middleton">Lefkos T. Middleton</name><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha A." last="Nance">Martha A. Nance</name><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia A." last="Oliveira">Sofia A. Oliveira</name><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><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><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen D." last="Roses">Allen D. Roses</name><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann M." last="Saunders">Ann M. Saunders</name><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald E." last="Schmechel">Donald E. Schmechel</name><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. Scott</name><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary W." last="Small">Gary W. Small</name><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith E." last="Stenger">Judith E. Stenger</name><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew B." last="Stern">Mathew B. Stern</name><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L." last="Watts">Ray L. Watts</name><name sortKey="Xu, Puting" sort="Xu, Puting" uniqKey="Xu P" first="Puting" last="Xu">Puting Xu</name></noCountry><country name="États-Unis"><region name="Texas"><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name></region><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L." last="Haines">Jonathan L. Haines</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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