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.