Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases.
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.
Li
Yi-Ju
YJ
Department of Medicine and Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA. yiju.li@duke.edu
Scott
William K
WK
Zhang
Ling
L
Lin
Ping-I
PI
Oliveira
Sofia A
SA
Skelly
Tara
T
Doraiswamy
Maurali P
MP
Welsh-Bohmer
Kathleen A
KA
Martin
Eden R
ER
Haines
Jonathan L
JL
Pericak-Vance
Margaret A
MA
Vance
Jeffery M
JM
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000453:epidemiology* / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000201:enzymology* / Q000453:epidemiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
C490476:GSTO1 protein, human; D005982:Glutathione Transferase