Glutathione peroxidase 1 (GPX1) single nucleotide polymorphism Pro198→Leu: Association with life span and coronary artery disease

Abstract

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% (χ 2 = 5.228, p = 0.022; OR =1.46), and in men who died early from cardiovascular diseases, 38.16% (χ 2 = 6.461, p = 0.011; OR = 1.69) compared to men in the control group, 26.8%. Moreover, a significantly higher gen otype 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% (χ 2 = 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% (χ 2 = 8.07, p = 0.0045), and from the subgroup with coronary artery disease with myocardial infarction before age 50, which was 19.44% (χ 2 = 14.49, p = 0.0001). Thus, our results indicate that the TT allele (Leu) of GPX1 Pro198→Leu (C > T) polymorphism is unfavor able for successful aging; it leads to predisposition to coronary artery disease, early myocardial infarction (before age 50), and early death (before age 55).

The importance of polymorphisms of regulatory and catalytic antioxidant proteins in chronic kidney disease

“…Of a particular importance is the functional GPX1 rs1050450 polymorphism, which induces C > T substitution changing the amino acid proline (Pro) with leucine (Leu) at position 198 (GPX1 Pro198Leu genotype) (64). The Leu allele of GPX1 gene confers with significantly impaired enzyme activity, which was found in vitro and also confirmed in humans (35,79). Moreover, Leu allele makes this enzyme less responsive to an increase in selenium (80).…”

“…Several isozymes of glutathione peroxidase family that vary in cellular location and substrate specificity have been identified so far (17,77). GPX1 is the most abundant isozyme in the glutathione peroxidases family (17,35,77). This enzyme is cytosolic and produced in all tissues (17,64,77).…”

“…Excessive oxidative stress in patients with CKD could be related to specific genetic patterns (17). Namely, genetic polymorphisms of regulatory (nuclear factor erythroid 2-related factor 2 (Nrf2)) and catalytic antioxidant proteins (SOD2 and GPX1) result in alteration in their proteins activity profile, hence affecting individuals antioxidant capacity (33)(34)(35)(36). In this comprehensive review, the focus was on the studies examining significance and roles of single nucleotide polymorphisms (SNPs) of Nrf2, SOD2 and GPX1 genes in CKD susceptibility and prognosis, outlining their importance and potential for clinical application.…”

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort

“…Among the first results in the field of antioxidant protection in COVID-19 were data on reduced erythrocyte activity of glutathione peroxidase, catalase, and superoxide dismutase in these patients compared to healthy individuals [ 21 ]. We hypothesized that variant GPX1 allele would potentiate this reduction in activity, since purified GPX1* Leu variant has been shown to possess lower enzymatic activity compared to the GPX1 *Pro enzyme [ 16 ]. Besides, particular importance of GPX1 in COVID-19 infection was suggested by the findings that GPX1 can function as a binding partner for main protease of SARS-CoV-2 virus (Mpro) [ 22 ].…”