Relationship between polymorphism rs1546155 of the GGT7 gene and the risk of ischemic stroke

Background: Since oxidative stress plays a role in the pathogenesis of ischemic stroke (IS), it is important to investigate the molecular mechanisms contributing to redox homeostasis and glutathione metabolism. The aim of the study: To analyze the association of the rs11546155 polymorphism of gamma-glutamyltransferase 7 (GGT7) gene with the risk of ischemic stroke. Materials and methods: DNA samples from 600 patients with IS and 688 controls were used for genotyping SNP rs11546155 by real-time PCR with allele discrimination using TaqMan probes. Results: It was found that genotypes G/A and A/A are associated with an increased risk of IS in females (OR=1.54, 95%CI 1.02–2.32, Pperm=0.04), while no associations between rs11546155 genotypes were observed in males. In patients with hypodynamia, the rs11546155 polymorphism was associated with an increased risk of IS (OR=1.59, 95%CI 1.01–2.00, Pperm=0.04), while in individuals with normal and increased physical activity, the SNP did not influence disease risk. Moreover, the carriers of allele rs11546155G who did not abuse alcohol possess a decreased risk of IS (OR = 1.59, 95%CI 1.012.00, Pperm = 0.04), while the protective effect of the allele against disease risk was not seen in alcohol abusers. Functional SNP annotation showed that the IS-related rs11546155A allele is associated with decreased expression of the GGT7 gene, as well as genes involved in autophagy and proteasomal protein degradation. Conclusion: This study was the first to establish the association of the rs11546155 polymorphism with the risk of IS. Further studies are needed to clarify the nature of the sex-specific SNP association and gene-environment interactions.