Role of the genes of glutathione-related enzymes involved in the antioxidant defense in survival and longevity
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 thegenes 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
Erdman VV, Tuktarova IA, Petintseva AA, et al. Role of the genes of glutathionerelated enzymes involved in the antioxidant defense in survival and longevity.
Research Results in Biomedicine. 2026;12(3):393-413. Russian.
DOI: 10.18413/2658-6533-2026-12-3-0-3
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