4.5 Article

Gene variations in GSTM3 are a risk factor for Alzheimer's disease

期刊

NEUROBIOLOGY OF AGING
卷 30, 期 5, 页码 691-696

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2007.08.012

关键词

Alzheimer's disease; Oxidative stress; GSTM3; Genetic risk factor

资金

  1. German Research Foundation [KO 2327/2-1, HE 2748/5]

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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); rs 1799735 (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. (C) 2007 Elsevier Inc. All fights reserved.

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