Polymorphisms in glutathione S-transferase omega-1 gene and increased risk of sporadic Alzheimer disease

Abstract

Previous studies examining the association between the glutathione S-transferase omega-1 (GSTO1) single-nucleotide polymorphisms (SNPs) and Alzheimer disease (AD) have yielded conflicting results. Furthermore, an effect of GSTO1 rs4925 on the age-at-onset (AAO) of AD was found in different studies on sporadic and familial AD cases, but with contrasting findings. A total sample of 103 AD patients, and 157 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotyped for the apolipoprotein E (APOE) polymorphism and the GSTO1 rs4925 and rs1804834 SNPs. Furthermore, we performed a haplotype analysis on these two SNPs on the GSTO1 locus and evaluated the possibility of interaction with APOE. Significant differences were observed in rs4925 genotype distribution between AD patients and age- and sex-matched healthy controls. Both the C/A (odds ratio [OR] = 3.116; 95% confidence interval [CI], 1.749-5.550) and the A/A (OR = 10.802; 95% CI, 3.605-32.128) genotypes resulted in an association with AD. A higher frequency of the allele A was observed in AD patients than in age- and sex-matched controls (OR = 3.789; 95% CI, 2.442-5.878). No significant differences were observed in the rs1804834 genotype or allele frequencies between AD patients and controls. No significant influence of the GSTO1 genotypes on the AAO was observed. No significant interaction was found among the GSTO1 SNPs and APOE. In both AD and controls, no important linkage disequilibrium (LD) was observed among the markers investigated. Whereas the C-A haplotype appeared to be protective against AD (OR = 0.303; 95% CI, 0.204-0.451), the A-A haplotype appeared to be at increased risk for AD (OR = 4.014,; 95% CI, 2.528-6.382). Our findings supported a role of the GSTO1 rs4925 SNP in the risk of sporadic AD in southern Italy, suggesting that this and other variants of the GSTO1 gene could be implicated in AD pathogenesis. © 2010 Mary Ann Liebert, Inc.