Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.

TitleGlutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.
Publication TypeJournal Article
Year of Publication2003
AuthorsLi, Y-J, Oliveira, SA, Xu, P, Martin, ER, Stenger, JE, Scherzer, CR, Hauser, MA, Scott, WK, Small, GW, Nance, MA, Watts, RL, Hubble, JP, Koller, WC, Pahwa, R, Stern, MB, Hiner, BC, Jankovic, J, Goetz, CG, Mastaglia, F, Middleton, LT, Roses, AD, Saunders, AM, Schmechel, DE, Gullans, SR, Haines, JL, Gilbert, JR, Vance, JM, Pericak-Vance, MA, Hulette, C, Welsh-Bohmer, KA
JournalHum Mol Genet
Volume12
Issue24
Pagination3259-67
Date Published2003 Dec 15
ISSN0964-6906
KeywordsAge of Onset, Aged, Alzheimer Disease, Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Glutathione Transferase, Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Parkinson Disease, 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.

DOI10.1093/hmg/ddg357
Alternate JournalHum. Mol. Genet.
PubMed ID14570706
Grant ListRR00865 / RR / NCRR NIH HHS / United States
AG13308 / AG / NIA NIH HHS / United States
MH59528 / MH / NIMH NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
MH52453 / MH / NIMH NIH HHS / United States
AG05128 / AG / NIA NIH HHS / United States
NS26630 / NS / NINDS NIH HHS / United States
NS39764 / NS / NINDS NIH HHS / United States
AG10123 / AG / NIA NIH HHS / United States
NS31153 / NS / NINDS NIH HHS / United States
AG11268 / AG / NIA NIH HHS / United States
NS031153 / NS / NINDS NIH HHS / United States
AG19085 / AG / NIA NIH HHS / United States