Gene variations in GSTM3 are a risk factor for Alzheimer's disease.
Oxidative stress is a relevant pathomechanism in Alzheimer's disease (AD) and gene variations in the glutathione S-transferase M3 gene (GSTM3), involved in the detoxification of oxygen radicals, might influence the risk of AD. We investigated the effect of three polymorphisms in GSTM3: rs1332018 (C/A); rs1799735 (del/AGG); rs7483 (G/A), on the risk of AD in 363 AD patients and 358 healthy controls. Single marker association analyses revealed that the AGG/AGG genotype of the GSTM3 rs1799735 (del/AGG) polymorphism was associated with an increased risk of AD (p=0.05), especially in the group of APOE4-allele non-carriers (p=0.004; OR=2.07). Examination of the haplotypes identified a two-marker haplotype (C/AGG) consisting of rs1332018 (C/A) and rs1799735 (del/AGG) to increase the risk of AD (p=0.029), this effect was also most prevalent in APOE4-allele non-carriers (p=0.009; OR=1.95). The population attributable risk of this haplotype in APOE4-allele non-carriers was 32.2%. Our results suggest that there is a group of AD patients in which variations in metabolism of oxidative stress play an important role.
Hong
G-S
GS
Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Heun
R
R
Jessen
F
F
Popp
J
J
Hentschel
F
F
Kelemen
P
P
Schulz
A
A
Maier
W
W
Kölsch
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000201:enzymology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D053327:Apolipoprotein E4; D005819:Genetic Markers; C483009:GSTM3 protein, human; D005982:Glutathione Transferase