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 1.01–2.00, 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
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 1.01–2.00, 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
we express our gratitude for the opportunity to conduct scientific work to the leadership of Kursk State Medical University in the person of the rector, Professor V.A. Lazarenko, Research Institute of Genetic and Molecular Epidemiology of Kursk State Medical University, in particular director, professor A.V. Polonikov