Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu polymorphism and stenosis of coronary arteries: A population-based prediction

Abstract

BackgroundWe studied the association between erythrocyte glutathione peroxidase1 (GPx1) activity and rs1050450 (Pro198Leu) site with the stenosis of coronary arteries and, evaluated the Pro/Leu position within the predicted tertiary structure.MethodsSubjects were recruited from who underwent coronary angiography (controls; n = 55, Stenosis < 5% and Patients; n = 95, Stenosis ≥ 50%). The GPx1 activity and rs1050450 C/T variants were determined using enzyme assay and RFLP-PCR techniques, respectively. The conserved regions and GPx1 tertiary structure were predicted using bioinformatics tools.ResultsWe did not find significant association between GPx1 activity (P = 0.96), rs1050450 genotype distribution and coronary artery disease (adjusted OR = 0.79; 95%CI 0.28–2.2, P = 0.6). The polymorphic variants were not located at the predicted structural and functional domains so that it had not the significant role on the GPx1stability and function.ConclusionsIn agreement with the results predicted from bioinformatics tools, we suggested that the GPx1 activity and rs1050450 (Pro198Leu) site are not involved in the development of stenosis of coronary arteries in the study population.

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

“…In this study, in addition to polymorphism association to CHD risk, we investigated the SOD and GPx activities in CHD subjects. Consistent with our results some studies suggested an association between SOD activity [ 34 ] but not GPx activity [ 31 , 46 , 47 ] with cardiopathy events. In contrast, others proposed the opposite [ 50 – 52 ].…”

“…Indeed, in a French population, Charniot et al [ 46 ] declared that GPx—variants influenced neither GPx activity nor cardiac events. Moreover, in a recent study of Iranian population, Najafi et al [ 47 ] showed that GPx1 activity and rs1050450 (Pro198Leu) site are not involved in the development of coronary artery stenosis. However, in disagreement with our data, other studies performed on Asian population demonstrated an association of GPx1 variant genotypes to CHD risk and carotid artery intra-media thickness (IMT).…”

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

“…In vitro studies GPx1 Pro198Leu studies revealed that GPx1 activity is significantly lower in the transfected bovine aortic endothelial cells expressing 198Leu variant, compared with those expressing 198Pro variant . The studies conducted on human showed different results; for instance, some studies reported a significant association between GPx1 Pro198Leu polymorphism and bladder cancer, prostate cancer, hepatocellular carcinoma, and also breast cancer; although consistent with our results no association has been found between this polymorphism and coronary heart disease, Familial mediterranean fever, gastric cancer, colorectal cancer, and basal cell carcinoma…”

Association of polymorphisms in genes coding for antioxidant enzymes and human male infertility

“…In the Pro200Leu polymorphism, there is a substitution of Pro to Leu at codon 200 located in the c-terminal region of the protein. Najafi, Ghasemi, Roustazadeh and Farajollahi (2014) in a computer predictor study concluded that this polymorphism is located on the protein surface in a nonfunctional region and that the substitution does not affect protein stability or structure. However, Hu and Diamond (2003) concluded that the Leu allele is less effective than the Pro allele when neutralizing peroxide radicals; in contrast with this observation, our results showed a higher presence of the Leu allele in fertile donors than in patients and better values for almost all the parameters in the traditional sperm analysis in the Leu/Leu genotype group (the only parameter differing was the volume).…”