Association between 242C>T polymorphism of NADPH oxidase p22phox gene (CYBA) and longevity in Russian population

Life span depends on many factors, including the level of reactive oxygen species, like superoxide radical. Superoxide radical is produced from oxygen in the course of the oxidation of NADPH to NADP⁺. The process is catalyzed by NADPH oxidase. In this study, genotype and allele distributions of the C242T (rs4673) polymorphism in the CYBA gene, which encodes the α subunit of NADPH oxidase (p22phox), were examined in the sample of long livers and in the population sample of the city of Tomsk. Statistically significantly higher frequency of T allele among female long livers (34.625%), compared to the females from Russian population (26.32%) was demonstrated (χ² = 5.226; p = 0.022; OR = 1.48). Thus, the T allele is associated with a high life expectancy in females from the Russian population. No such association was observed for males from the same population.     

The glutathione peroxidase 1 (GPX1) single nucleotide polymorphism pro198Leu: association with life span and coronary artery disease

In this study we genotyped polymorphism in GPX1 Pro198Leu (C > T) rs 1050450 in four groups: patients with coronary artery disease, long-livers - above 90 years, early died peoples (before 55 years) from cardiovascular diseases and Russian population as control group. We have found significant higher allele T frequency in men with coronary artery disease -34.84% (Chi2 = 5.228, p = 0.022; OR = 1.46) and in early died men from cardiovascular diseases--38.16% (Chi2 = 6.461, p = 0.011; OR = 1.69) compared with control men--26.8%. Moreover, significantly higher genotype TT frequency has been shown in patients with coronary artery disease and myocardial infarction before age 50--19.44% in comparison with control group--7.28% (Chi2 = 9.55, p = 0.002). The TT frequency in long-livers (4.39%) was the lowest and significantly different from coronary artery disease group--12.79% (Chi2 = 8.07, p = 0.0045) and from coronary artery disease subgroup with myocardial infarction before 50--19.44% (Chi2 = 14.49, p = 0.0001). Thus our results indicate that allele T (Leu) of GPX1 Pro198Leu (C > T) polymorphism is unfavorable for successful ageing. It predisposes to coronary heart disease, earlier myocardial infarction (before age 50) and earlier death (before age 55).     

Glutathione peroxidase 1 (<Emphasis Type="Italic">GPX1</Emphasis>) single nucleotide polymorphism Pro198→Leu: Association with life span and coronary artery disease

In this study, we genotyped polymorphism in GPX1 Pro198→Leu (C→T) rs 1050450 in four groups, i.e., patients with coronary artery disease, people who lived a long time (over 90 years), people who died early (before 55 years) from cardiovascular disease, and the Russian population as a control group. We have found a significant higher T-allele frequency in men with coronary artery disease, i.e., 34.84% (χ² = 5.228, p = 0.022; OR =1.46), and in men who died early from cardiovascular diseases, 38.16% (χ² = 6.461, p = 0.011; OR = 1.69) compared to men in the control group, 26.8%. Moreover, a significantly higher genotype TT frequency has been shown in patients with coronary artery disease and myocardial infarction before age 50, which is 19.44% compared to the control group, which was 7.28% (χ² = 9.55, p = 0.002). The TT frequency in individuals who lived a long time (4.39%) was the lowest and differed significantly from the group with coronary artery disease, which was 12.79% (χ² = 8.07, p = 0.0045), and from the subgroup with coronary artery disease with myocardial infarction before age 50, which was 19.44% (χ² = 14.49, p = 0.0001). Thus, our results indicate that the TT allele (Leu) of GPX1 Pro198→Leu (C > T) polymorphism is unfavorable for successful aging; it leads to predisposition to coronary artery disease, early myocardial infarction (before age 50), and early death (before age 55).