Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases.

TitleRevealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases.
Publication TypeJournal Article
Year of Publication2006
AuthorsLi, Y-J, Scott, WK, Zhang, L, Lin, P-I, Oliveira, SA, Skelly, T, Doraiswamy, MP, Welsh-Bohmer, KA, Martin, ER, Haines, JL, Pericak-Vance, MA, Vance, JM
JournalNeurobiol Aging
Volume27
Issue8
Pagination1087-93
Date Published2006 Aug
ISSN1558-1497
KeywordsAge of Onset, Aged, Aged, 80 and over, Alzheimer Disease, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Genetic Testing, Glutathione Transferase, Heterozygote, Humans, Incidence, Male, Middle Aged, Parkinson Disease, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, United States
Abstract

We previously reported a linkage region on chromosome 10q for age-at-onset (AAO) of Alzheimer (AD) and Parkinson (PD) diseases. Glutathione S-transferase, omega-1 (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then reported to associate with AAO of AD and PD. To examine whether GSTO1 and GSTO2 (hereafter referred to as GSTO1h) are responsible for the linkage evidence, we identified 39 families in AD that lead to our previous linkage and association findings. The evidence of linkage and association was markedly diminished after removing these 39 families from the analyses, thus providing support that GSTO1h drives the original linkage results. The maximum average AAO delayed by GSTO1h SNP 7-1 (rs4825, A nucleotide) was 6.8 (+/-4.41) years for AD and 8.6(+/-5.71) for PD, respectively. This is comparable to the magnitude of AAO difference by APOE-4 in these same AD and PD families. These findings suggest the presence of genetic heterogeneity for GSTO1h's effect on AAO, and support GSTO1h's role in modifying AAO in these two disorders.

DOI10.1016/j.neurobiolaging.2005.05.013
Alternate JournalNeurobiol. Aging
PubMed ID15985314
PubMed Central IDPMC1482739
Grant ListAG19757 / AG / NIA NIH HHS / United States
P50 AG005128 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
U01 MH046373 / MH / NIMH NIH HHS / United States
NS311530 / NS / NINDS NIH HHS / United States
AG05128 / AG / NIA NIH HHS / United States
R01 NS031153 / NS / NINDS NIH HHS / United States
U01 MH046290 / MH / NIMH NIH HHS / United States
R01 AG021547 / AG / NIA NIH HHS / United States
R01 AG019757 / AG / NIA NIH HHS / United States
AG021547 / AG / NIA NIH HHS / United States
U01 MH046281 / MH / NIMH NIH HHS / United States