Abstract
Objectives: The current study aimed to determine whether genetic differences in the tumor necrosis factor-alpha (TNF alpha) and prostaglandin-endoperoxide synthase 2 (PTG2) genes are linked to type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN).Background: DN is a major cause of chronic kidney disease (CKD). Unfortunately, the precise pathogenic mechanisms of DN are not completely understood. Recent data suggest a link between inflammatory cytokines and the chronic complications of T2DM. TNF-alpha and PTG2 are key mediators of inflammation. Subjects and methods: This is a case-control study that includes 100 patients (group 1: 50 diabetic patients with diabetic nephropathy and group 2: 50 patients without diabetic nephropathy) and 50 age- and sex-matched healthy controls (group 3). Genotyping of TNF-alpha (rs3651525) and PTGS2 (rs689466) by real-time PCR was applied. Results: TNF-alpha (rs3651525) and PTGS2 (rs689466) genotype frequency and allelic distribution are in HardyWeinberg equilibrium (HWE). When T2DM patients with nephropathy were compared to those without DN, regression analysis for the PTGS2 rs689466 and TNF-rs361525 single nucleotide polymorphisms (SNPs) demonstrated that none of the SNP genotypes showed a major risk factor for DN susceptibility. As regards TNF-alpha rs361525, GA and AA genotypes were significantly associated with a higher risk of T2DM when compared to GG, and A allele showed a 3.721-fold increased risk. TNF-alpha rs361525 AA genotype (OR, 10.980; 95% CI 1.385-87.066) and TNF-rs361525 GA genotype (OR, 3.050; 95% CI 1.315-7.0758) are the most substantially linked parameters with the risk of diabetes mellitus in univariate analysis.According to the multivariate analysis, the AA and GA genotypes of the SNP rs361525 significantly affect the development of diabetes mellitus. No remarkable association was found between the PTGS2 (rs689466) polymorphism and diabetes mellitus and diabetic nephropathy. Conclusion: In contrast to the lack of a significant correlation between PTGS2 (rs689466) and DM or DN, TNF-alpha rs361525 was connected to the possibility of developing diabetes mellitus in our study.