Journal article
Glutathione S-transferase omega-1 modifiesage-at-onset of Alzheimer disease and Parkinson disease
Human Molecular Genetics, Vol.12(24), pp.3259-3267
2003
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.
Details
- Title
- Glutathione S-transferase omega-1 modifiesage-at-onset of Alzheimer disease and Parkinson disease
- Authors/Creators
- Y-J Li (Author/Creator) - Duke UniversityS.A. Oliveira (Author/Creator) - Duke UniversityP. Xu (Author/Creator) - Duke UniversityE.R. Martin (Author/Creator) - Duke UniversityJ.E. Stenger (Author/Creator) - Duke UniversityC.R. Scherzer (Author/Creator) - Harvard UniversityM.A. Hauser (Author/Creator) - Duke UniversityW.K. Scott (Author/Creator) - Duke UniversityG.W. Small (Author/Creator) - University of California, Los AngelesM.A. Nance (Author/Creator) - Struthers Parkinson CenterR.L. Watts (Author/Creator) - Emory UniversityJ.P. Hubble (Author/Creator) - The Ohio State UniversityW.C. Koller (Author/Creator) - University of Miami*R. Pahwa (Author/Creator) - University of KansasM.B. Stern (Author/Creator) - University of PennsylvaniaB.C. Hiner (Author/Creator) - Marshfield ClinicJ. Jankovic (Author/Creator) - Baylor College of MedicineC.G. Goetz (Author/Creator) - Rush UniversityF. Mastaglia (Author/Creator) - The University of Western AustraliaL.T. Middleton (Author/Creator) - GlaxoSmithKline Research/DevelopmentA.D. Roses (Author/Creator) - (GlaxoSmithKline)A.M. Saunders (Author/Creator) - (GlaxoSmithKline)D.E. Schmechel (Author/Creator) - Duke UniversityS.R. Gullans (Author/Creator) - Harvard UniversityJ.L. Haines (Author/Creator) - Vanderbilt UniversityJ.R. Gilbert (Author/Creator) - Duke UniversityJ.M. Vance (Author/Creator) - Duke UniversityM.A. Pericak-Vance (Author/Creator) - Duke University
- Publication Details
- Human Molecular Genetics, Vol.12(24), pp.3259-3267
- Publisher
- Oxford University Press
- Identifiers
- 991005540335107891
- Copyright
- 2003 Oxford University Press
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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