Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa 450054, Russia.
Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa 450054, Russia.
Gene. 2024 Aug 15;919:148510. doi: 10.1016/j.gene.2024.148510. Epub 2024 Apr 26.
Genetic background of healthy or pathological styles of aging and human lifespan is determined by joint gene interactions. Lucky combinations of antioxidant gene polymorphisms can result in a highly adaptive phenotype, providing a successful way to interact with external triggers. Our purpose was to identify the polygenic markers of survival and longevity in the antioxidant genes among elderly people with physiological and pathological aging.
In a 20-year follow-up study of 2350 individuals aged 18-114 years residing in the Volga-Ural region of Russia, sex-adjusted association analyses of MTHFR rs1801133, MSRA rs10098474, PON1 rs662, PON2 rs7493, SOD1 rs2070424, NQO1 rs1131341 and CAT rs1001179 polymorphic loci with longevity were carried out. Survival analysis was subsequently performed using the established single genes and gene-gene combinations as cofactors.
The PON1 rs662G allele was defined as the main longevity marker in women (OR = 1.44, p = 3E-04 in the log-additive model; HR = 0.77, p = 1.9E-04 in the Cox-survival model). The polymorphisms in the MTHFR, MSRA, PON2, SOD1, and CAT genes had an additive effect on longevity. A strong protective effect of combined MTHFR rs1801133C, MSRA rs10098474T, PON1 rs662G, and PON2 rs7493C alleles against mortality was obtained in women (HR = 0.81, p = 5E-03). The PON1 rs662A allele had a meaningful impact on mortality for both long-lived men with cerebrovascular accidents (HR = 1.76, p = 0.027 for the PON1 rs662AG genotype) and women with cardiovascular diseases (HR = 1.43, p = 0.002 for PON1 rs662AA genotype). The MTHFR rs1801133TT (HR = 1.91, p = 0.036), CAT rs1001179TT (HR = 2.83, p = 0.031) and SOD1 rs2070424*AG (HR = 1.58, p = 0.018) genotypes were associated with the cancer mortality.
In our longitudinal 20-year study, we found the combinations of functional polymorphisms in antioxidant genes involved in longevity and survival in certain clinical phenotypes in the advanced age.
健康或病理性衰老风格和人类寿命的遗传背景由联合基因相互作用决定。抗氧化基因多态性的幸运组合可以产生高度适应的表型，为与外部触发因素相互作用提供了成功的途径。我们的目的是在生理和病理性衰老的老年人中识别抗氧化基因中与生存和长寿相关的多基因标记。
在对居住在俄罗斯伏尔加-乌拉尔地区的 2350 名 18-114 岁的个体进行了 20 年的随访研究中，我们对 MTHFR rs1801133、MSRA rs10098474、PON1 rs662、PON2 rs7493、SOD1 rs2070424、NQO1 rs1131341 和 CAT rs1001179 多态性位点与长寿的性别调整关联进行了分析。随后使用建立的单基因和基因-基因组合作为协变量进行生存分析。
PON1 rs662G 等位基因被定义为女性的主要长寿标记物（对数加性模型中的 OR=1.44，p=3E-04；Cox 生存模型中的 HR=0.77，p=1.9E-04）。MTHFR、MSRA、PON2、SOD1 和 CAT 基因的多态性对长寿具有累加效应。在女性中，获得了 MTHFR rs1801133C、MSRA rs10098474T、PON1 rs662G 和 PON2 rs7493C 等位基因对死亡率的强烈保护作用（HR=0.81，p=5E-03）。PON1 rs662A 等位基因对男性的脑血管意外（PON1 rs662AG 基因型的 HR=1.76，p=0.027）和女性的心血管疾病（PON1 rs662AA 基因型的 HR=1.43，p=0.002）的死亡率有重要影响。MTHFR rs1801133TT（HR=1.91，p=0.036）、CAT rs1001179TT（HR=2.83，p=0.031）和 SOD1 rs2070424*AG（HR=1.58，p=0.018）基因型与癌症死亡率相关。
在我们的 20 年纵向研究中，我们发现了抗氧化基因中的功能多态性组合与某些临床表型的老年长寿和生存相关。
