Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Identifieur interne : 001421 ( Main/Exploration ); précédent : 001420; suivant : 001422Glutathione 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 [États-Unis] ; 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.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Age of Onset, Aged, Alzheimer Disease (enzymology), Alzheimer Disease (genetics), Alzheimer disease, Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Glutathione Transferase (genetics), Glutathione Transferase (metabolism), Glutathione transferase, Human, Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Molecular biology, Oligonucleotide Array Sequence Analysis, Onset time, Parkinson Disease (enzymology), Parkinson Disease (genetics), Parkinson disease, Polymorphism, Single Nucleotide.
- MESH :
- chemical , genetics : Glutathione Transferase.
- enzymology : Alzheimer Disease, Parkinson Disease.
- genetics : Alzheimer Disease, Parkinson Disease.
- chemical , metabolism : Glutathione Transferase.
- Age of Onset, Aged, Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide.
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.
Url:
DOI: 10.1093/hmg/ddg357
Affiliations:
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Le document en format XML
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Martin</name><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><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><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><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><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><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><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><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><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><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><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><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><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><wicri:noCountry code="subField"></wicri:noCountry><country>États-Unis</country><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university" n="3">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name><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><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><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><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><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><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><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="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" last="Gilbert">John 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" last="Vance">Jeffery 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" last="Pericak">Margaret Pericak</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></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age of Onset</term><term>Aged</term><term>Alzheimer Disease (enzymology)</term><term>Alzheimer Disease (genetics)</term><term>Alzheimer disease</term><term>Chromosome Mapping</term><term>Chromosomes, Human, Pair 10</term><term>Female</term><term>Glutathione Transferase (genetics)</term><term>Glutathione Transferase (metabolism)</term><term>Glutathione transferase</term><term>Human</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Lod Score</term><term>Male</term><term>Middle Aged</term><term>Molecular biology</term><term>Oligonucleotide Array Sequence Analysis</term><term>Onset time</term><term>Parkinson Disease (enzymology)</term><term>Parkinson Disease (genetics)</term><term>Parkinson disease</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutathione Transferase</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Alzheimer Disease</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutathione Transferase</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Age of Onset</term><term>Aged</term><term>Chromosome Mapping</term><term>Chromosomes, Human, Pair 10</term><term>Female</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Lod Score</term><term>Male</term><term>Middle Aged</term><term>Oligonucleotide Array Sequence Analysis</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Biologie moléculaire</term><term>Démence Alzheimer</term><term>Glutathione transferase</term><term>Homme</term><term>Parkinson maladie</term><term>Temps établissement</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></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" last="Gilbert">John Gilbert</name><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven" last="Gullans">Steven Gullans</name><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael" last="Hauser">Michael Hauser</name><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley" last="Hiner">Bradley Hiner</name><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean" last="Hubble">Jean Hubble</name><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden 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" last="Middleton">Lefkos Middleton</name><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia 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" last="Pericak">Margaret Pericak</name><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen" last="Roses">Allen Roses</name><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann" last="Saunders">Ann Saunders</name><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens" last="Scherzer">Clemens Scherzer</name><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald Schmechel</name><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary" last="Small">Gary Small</name><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith" last="Stenger">Judith Stenger</name><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew" last="Stern">Mathew Stern</name><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray 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" last="Haines">Jonathan Haines</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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