ABSTRACT
Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is associated with reduced enzyme activity. The aim of this study was to evaluate the association between Pro198Leu polymorphism and risk of diabetic peripheral neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In the patient group, 33 % had diabetic peripheral neuropathy. All subjects were genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction and restriction analysis. A significant increase in the T allele and TT genotype frequencies was observed in DPN patients compared to those without DPN (OR 1.55, 95 % CI 1.30-1.85 and 1.89, 95 % CI 1.30-2.74, respectively). The association remained significant after correction for age, disease duration, HbA1c and BMI. When distribution of T allele was compared between DPN+ and DPN- subgroups and controls, OR was 1.54 for DPN+ and 1.00 for DPN- patients. In conclusion, our findings suggest that Gpx1 Pro198Leu genotypes are significantly associated with the risk of diabetic peripheral neuropathy in patients with T2DM. The study provides new clinically relevant information regarding genetic determinants of susceptibility to diabetic neuropathy.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetic Neuropathies/genetics , Glutathione Peroxidase/genetics , Polymorphism, Single Nucleotide , Age of Onset , Aged , Alleles , Cardiovascular Diseases/epidemiology , Case-Control Studies , Comorbidity , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetic Neuropathies/enzymology , Diabetic Neuropathies/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Glutathione Peroxidase/physiology , Glycated Hemoglobin/analysis , Humans , Hyperlipidemias/epidemiology , Male , Middle Aged , Poland/epidemiology , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Glutathione Peroxidase GPX1ABSTRACT
BACKGROUND: Glutathione peroxidase-1 (GPX-1) activity was reported to be useful marker for monitoring cardiovascular disease. However, accurate assessment of coronary artery disease (CAD) using GPX-1 polymorphism is limited for South Asian population. Present study aim to assess GPX-1activity and GPX-1 polymorphismin patients with coronary artery disease (CAD) who were confirmed with coronary angiography findings and in apparently healthy subjects. METHODS: Case control study was carried out with 85 patients (58 males and 27 females) 40-60 years of age confirmed as having CAD on coronary angiography findings and 85 age and sex matched healthy volunteers as controls. Blood samples were analyzed for erythrocyte GPX-1 activity and GPX-1 polymorphism in both groups and the severity of CAD was assessed using coronary angiography scoring system based on vessel, stenosis and extent score. RESULTS: Coronary angiography scores indicated that erythrocyteGPX-1 cutoff value of 23.9 U/gHb showed a high sensitivity and negative predictive value in ruling out major vessel disease. The GPX-1 Pro198Leu (CT) polymorphism was higher in patients with CAD (25.3 %) when compared to controls (10.7 %). Pro198Leu (CT) genotype showed a 2.84 fold risk for CAD [odds ratio 2.84 (95 % CI 1.15-6.98), p = 0.019]. CONCLUSION: Coronary angiography findings indicated that individuals possessing Pro198Leu (CT) polymorphism were found to be associated with low erythrocyte GPX-1 activity and increased susceptibility for CAD.
Subject(s)
Coronary Artery Disease/genetics , Coronary Stenosis/genetics , Erythrocytes/enzymology , Glutathione Peroxidase/genetics , Polymorphism, Genetic , Adult , Case-Control Studies , Chi-Square Distribution , Coronary Angiography , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/enzymology , Coronary Stenosis/blood , Coronary Stenosis/diagnosis , Coronary Stenosis/enzymology , Feasibility Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Glutathione Peroxidase/blood , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Phenotype , Risk Factors , Severity of Illness Index , Glutathione Peroxidase GPX1ABSTRACT
0.05).Genotype CT frequency in T2DM group was significantly increased when compared with non-DM control group(P=0.012,OR=2.254).Conclusion Pro198Leu polymorphism of GPX-1 gene increases the risk of type 2 diabetes in Han Chinese of Shanghai,while T allele is not a risk factor of diabetic CHD.
