1. Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases.
- Author
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Li YJ, Scott WK, Zhang L, Lin PI, Oliveira SA, Skelly T, Doraiswamy MP, Welsh-Bohmer KA, Martin ER, Haines JL, Pericak-Vance MA, and Vance JM
- Subjects
- Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease genetics, DNA Mutational Analysis methods, Female, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Heterozygote, Humans, Incidence, Male, Middle Aged, Parkinson Disease genetics, Polymorphism, Single Nucleotide genetics, Risk Factors, United States epidemiology, Alzheimer Disease enzymology, Alzheimer Disease epidemiology, Genetic Testing methods, Glutathione Transferase genetics, Parkinson Disease enzymology, Parkinson Disease epidemiology, Risk Assessment methods
- 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.
- Published
- 2006
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