MnSOD and GPx1 polymorphism relationship with coronary heart disease risk and severity

Abstract

BackgroundDisturbance of the equilibrium between reactive oxygen species (ROS) and anti-oxidants (AOX) has been implicated in various diseases, including atherosclerosis, the most common pathologic process underlying coronary heart disease (CHD). Thus, the defense systems against ROS are critical protecting blood vessel walls against oxidative damage. In this study, we investigate whether Ala16Val MnSOD and Pro198Leu GPx polymorphisms are associated with CHD susceptibility and/or severity.MethodsBoth polymorphisms were genotyped in a sample of 203 controls and 164 patients. CHD risk and severity, antioxidant status (enzymatic and/or non enzymatic) and biochemical parameters were assessed and analysed by genotype.ResultsA significant association of MnSOD variant to CHD risk was revealed in males. Males harboring the Val/Val genotype were approximately at twofold increased risk of CHD compared to controls (Ala carriers vs Val/Val, adjusted OR 1.89; 95 % CI 1.18‒3.42, p = 0.03). Significant decreases in SOD activity and total antioxidant status (TAS) were observed in Val carriers and by CHD status. Whereas, no association of GPx variant genotype (Leu/Leu) and activity to cardiopathy events was discerned. CHD severity, as demonstrated by the number of vessel stenosis, was associated with significantly higher frequency of Val allele and LDL levels in CHD subjects.ConclusionsOur results showed a lack of association of Pro198Leu GPx polymorphism to CHD risk and severity. However, they suggest that Ala16Val MnSOD polymorphism and decreased antioxidant defences are likely contributed to CHD risk in Tunisian men. Furthermore, the Val encoding MnSOD allele and decreased SOD activity were significantly correlated with CHD stenosis progression.

Association between Polymorphisms of Antioxidant Gene (Mnsod, CAT and Gpx1) and Risk of Coronary Artery Disease

“…They found that MnSOD Val/Val carriers were associated with higher carotid intimal media thickness, which indicates more severe atherosclerosis [28]. Souiden et al discovered an approximately twofold risk of CAD in Tunisian men harbouring the Val/Val genotype [22]. These results are inconsistent with our data.…”

“…This inconsistency may be due to the influence of interracial MnSOD Ala allele frequency difference. The higher frequency of Ala allele was found as 48.3% in Caucasians and 25.1% in Arabs, respectively [22,28]. It was a discrepancy compared to our Chinese population which was 7.83%.…”

“…Antioxidants defend cells against damage from free radicals and ROS, maintaining redox homeostasis. MnSOD, GPx1, and CAT are all endogenous enzymatic antioxidants [21,22]. In the current study, we focus on whether genetic polymorphisms of MnSOD, GPx1, and CAT affect vulnerability or severity of CAD in Taiwan.…”

No evidence for a major effect of three common polymorphisms of the GPx1, MnSOD, and CAT genes on PCOS susceptibility

“…It has been shown that the MnSOD Ala 16 Val polymorphism is associated with diabetic nephropathy in patients with type-2 diabetes, 39 diabetic nephropathy in patients with type 1 diabetes, 40 periodontitis disease, 41 and coronary heart disease. 32 There are growing numbers of publications on the −262C/T polymorphism of the catalase gene (rs1001179) in different populations and diseases; although there are GelRed on 2% agarose gel electrophoresis. Lane 1 and 2 shows homozygote "CC" genotype for the one person, Lane 3 and 4 shows heterozygote "CT" genotype for the second person, Lane 5 and 6 shows homozygote "TT" genotype for the third person C and Lane 7 Shows 50 bp DNA molecular markers no reports related to this polymorphism and PCOS.…”

The antioxidant effect of Brazil nut (Bertholletia excelsa) is influenced by a genetic superoxide-hydrogen peroxide imbalance in healthy humans

“…It is important to point out that the V allele also causes SA-HP imbalance, in particular, VV-SOD2 genotypes have been associated with the risk of some metabolic disorders, such as hypercholesterolemia, obesity, and cardiovascular diseases [32][33][34][35][36] and with type 2 diabetes mellitus complications. 37 The explanation for the increase in the susceptibility to these disorders in the VV genotype is that VV genotype cells maintain high basal SA levels that quickly react with nitric oxide (NO) producing extensive alterations in the cells because lipoperoxidation-derived protein carbonylation generates other ROS types.…”