期刊
MOLECULAR NEURODEGENERATION
卷 7, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1750-1326-7-13
关键词
GSTO genes; Disease risk; Gene expression; Association
资金
- National Institute of Health
- National Institute on Aging [R01 032990, R01 AG018023, AG025711, AG017216, AG003949]
- Mayo Alzheimer's Disease Research Center [P50 AG016574]
- Alzheimer's Disease Patient Registry [U01 AG006576]
- Robert and Clarice Smith
- Abigail Van Buren Alzheimer's Disease Research Program
- National Institutes of Health [KL2 RR024151]
- Siragusa Foundation
- NIH/NINDS [P50 NS072187-01 S2, NS057567, 1RC2NS070276]
- Mayo Clinic Florida (MCF) Research Committee
- Dystonia Medical Research Foundation
Background: Glutathione S-transferase omega-1 and 2 genes (GSTO1, GSTO2), residing within an Alzheimer and Parkinson disease (AD and PD) linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects). Results: We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 x 10(-11)-1.9 x 10(-27)), but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003). Conclusion: These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据