Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.
Identifieur interne : 000065 ( Ncbi/Checkpoint ); précédent : 000064; suivant : 000066Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.
Auteurs : Yi Li [États-Unis] ; 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 ; John. Gilbert ; Jeffery. Vance ; Margaret. Pericak ; Christine Hulette ; Kathleen. WelshSource :
- Human molecular genetics [ 0964-6906 ] ; 2003.
English descriptors
- KwdEn :
- Age of Onset, Aged, Alzheimer Disease (enzymology), Alzheimer Disease (genetics), Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Glutathione Transferase (genetics), Glutathione Transferase (metabolism), Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Parkinson Disease (enzymology), Parkinson Disease (genetics), 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-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.
DOI: 10.1093/hmg/ddg357
PubMed: 14570706
Affiliations:
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pubmed:14570706Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.</title>
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<author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan. Haines</name>
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<author><name sortKey="Hulette, Christine" sort="Hulette, Christine" uniqKey="Hulette C" first="Christine" last="Hulette">Christine Hulette</name>
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<author><name sortKey="Welsh Bohmer, Kathleen A" sort="Welsh Bohmer, Kathleen A" uniqKey="Welsh Bohmer K" first="Kathleen" last="Welsh">Kathleen. Welsh</name>
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<series><title level="j">Human molecular genetics</title>
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<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>Chromosome Mapping</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Female</term>
<term>Glutathione Transferase (genetics)</term>
<term>Glutathione Transferase (metabolism)</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>Parkinson Disease (enzymology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Polymorphism, Single Nucleotide</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutathione Transferase</term>
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<term>Parkinson Disease</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term>
<term>Parkinson Disease</term>
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<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>
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<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-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</div>
</front>
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<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="Welsh Bohmer, Kathleen A" sort="Welsh Bohmer, Kathleen A" uniqKey="Welsh Bohmer K" first="Kathleen" last="Welsh">Kathleen. Welsh</name>
<name sortKey="Xu, Puting" sort="Xu, Puting" uniqKey="Xu P" first="Puting" last="Xu">Puting Xu</name>
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<country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
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<name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
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