2658-6533Research Results in Biomedicine2658-653310.18413/2658-6533-2026-12-3-0-34264Genetics<strong>Role of the genes of glutathione-related enzymes involved in the antioxidant defense in survival and longevity</strong><br /> &nbsp;<strong>Role of the genes of glutathione-related enzymes involved in the antioxidant defense in survival and longevity</strong><br /> &nbsp;ErdmanVera V.ErdmanVera V.danivera@mail.ruTuktarovaIlsiar A.TuktarovaIlsiar A.iltuk@mail.ruPetintsevaAnna A.PetintsevaAnna A.anna_petinseva@mail.ruTimashevaYanina R.TimashevaYanina R.ianina_t@mail.ruNasibullinTimur R.NasibullinTimur R.nasibullintr@yandex.ru202612300

Background: Human longevity is characterized by maintaining cellular homeostasis in the age-related changes of the internal conditions. The efficiency of many redox endogenous processes depends on the structural and functional features of glutathione-related genes. The aim of the study: To study the role of the polymorphic loci GSR (rs1002149), GSTP1 (rs1695), GPX1 (rs1050450), GPX4 (rs713041) and GPX8 (rs381852) of genes encoding glutathione-related enzymes in survival and longevity during physiological and pathological aging. Materials and methods: A sample of 3218 individuals, Russians, Bashkirs and Tatars by ethnicity, was divided into three age groups of middle-aged (18-59 years), aged (60-89 years) persons and long-livers (90-114 years). Information on survival status and diagnosis was obtained for 1656 individuals aged over 45 years. Polymorphic genetic markers were analyzed using TaqMan PCR technology. Results: The genetic markers of longevity and survival were established. They included the GPX4 (rs713041) T allele (in men, OR=1.66, P=0.006; HR=0.81, P=0.02), the GPX4 (rs713041) CT genotype (in the total group, OR=1.33, P=0.004; for multimorbidity, HR=0.6, P=0.02), and the combination of GPX1 (rs1050450) G and GSTP1 (rs1695) A alleles (in Russian women, OR=4.15, PFDR=0.04; for the total group, HR=0.5, P=0.02). In Russians, the GPX8 (rs381852) A allele was associated with longevity among women (OR=2.52, P=0.005); in homozygous and heterozygous variants, it was found in nine longevity-promoting combinations, with the most statistical significance along with the GPX1 (rs1050450) G and GSTP1 (rs1695) A alleles (OR=4.07, PFDR=0.006). In Bashkirs, the combination of GPX1 (rs1050450) GG, GPX4 (rs713041) C and GSR (rs1002149) T was related with longevity (OR=7.98, PFDR=0.02). The GSR (rs1002149) TT genotype was linked to all-cause mortality (HR=1.47, P=0.02). The GPX1 (rs1050450) AG genotype (HR=1.42, P=0.003) and the GPX1 (rs1050450) G allele combined with the GSTP1 (rs1695) A allele (HR=1.4, P=0.02) predicted cerebrovascular mortality in the advanced age. Conclusion: In the genes of glutathione-related enzymes involved in the antioxidant defense, the genetic predictors of the overall survival in the advanced age, clinical-related mortality, and longevity were identified in generally and separately for each studied ethnic groups

Background: Human longevity is characterized by maintaining cellular homeostasis in the age-related changes of the internal conditions. The efficiency of many redox endogenous processes depends on the structural and functional features of glutathione-related genes. The aim of the study: To study the role of the polymorphic loci GSR (rs1002149), GSTP1 (rs1695), GPX1 (rs1050450), GPX4 (rs713041) and GPX8 (rs381852) of genes encoding glutathione-related enzymes in survival and longevity during physiological and pathological aging. Materials and methods: A sample of 3218 individuals, Russians, Bashkirs and Tatars by ethnicity, was divided into three age groups of middle-aged (18-59 years), aged (60-89 years) persons and long-livers (90-114 years). Information on survival status and diagnosis was obtained for 1656 individuals aged over 45 years. Polymorphic genetic markers were analyzed using TaqMan PCR technology. Results: The genetic markers of longevity and survival were established. They included the GPX4 (rs713041) T allele (in men, OR=1.66, P=0.006; HR=0.81, P=0.02), the GPX4 (rs713041) CT genotype (in the total group, OR=1.33, P=0.004; for multimorbidity, HR=0.6, P=0.02), and the combination of GPX1 (rs1050450) G and GSTP1 (rs1695) A alleles (in Russian women, OR=4.15, PFDR=0.04; for the total group, HR=0.5, P=0.02). In Russians, the GPX8 (rs381852) A allele was associated with longevity among women (OR=2.52, P=0.005); in homozygous and heterozygous variants, it was found in nine longevity-promoting combinations, with the most statistical significance along with the GPX1 (rs1050450) G and GSTP1 (rs1695) A alleles (OR=4.07, PFDR=0.006). In Bashkirs, the combination of GPX1 (rs1050450) GG, GPX4 (rs713041) C and GSR (rs1002149) T was related with longevity (OR=7.98, PFDR=0.02). The GSR (rs1002149) TT genotype was linked to all-cause mortality (HR=1.47, P=0.02). The GPX1 (rs1050450) AG genotype (HR=1.42, P=0.003) and the GPX1 (rs1050450) G allele combined with the GSTP1 (rs1695) A allele (HR=1.4, P=0.02) predicted cerebrovascular mortality in the advanced age. Conclusion: In the genes of glutathione-related enzymes involved in the antioxidant defense, the genetic predictors of the overall survival in the advanced age, clinical-related mortality, and longevity were identified in generally and separately for each studied ethnic groups

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