Association of NPHS2, PON1 and KCNJ11 Gene Polymorphisms with Diabetic Nephropathy

Purpose: Diabetic nephropathy (DN) affects almost 40% of diabetic patients and is clinically categorized by declining glomerular filtration rate, proteinuria and hypertension, ultimately leads to renal failure. Genome-wide association studies (GWAS) have identified several genetic loci associated with DN, including various genetic variants. This study was thus conducted to find an association of NPHS2, PON1 and KCNJ11 gene variants with the risk of DN. Method: This case-control study was performed in 300 unrelated subjects consisting of 150 DN patients and 150 controls that were age, sex and ethnicity matched. Genotyping was done using PCR-RFLP and primers amplification refractory mutation system-PCR approach. Results were analyzed using SPSSS ver.21 software. Result: In context to KCNJ11 , OR values for KK and EE genotypes were 4.163 (P<0.001) and 0.397( P=0.001 ), respectively. Frequencies of K and E alleles were 57.33% and 42.67% in DN cases as compared to 39% and 61% in controls (OR=2.101, 0.476). The OR values for K and E alleles were 2.101 (P<0.001) and 0.476 (P<0.001), respectively. In PON1 , the OR values for AA and GG genotypes were 0.66 (P=0.08) and 5.86 (P=0.011) respectively. The OR values for A and G alleles were 0.64 (P=0.021) and 1.569 (P=0.021) respectively. No significant association of NPHS2 gene was observed on comparing genotype and allele frequencies among cases and controls. Conclusion: KCNJ11 and PON1 genes could serve as genetic biomarkers for establishing DN susceptibility. Early identification of genetic risk factors in patients enables earlier intervention, eventually delaying and dropping the effect of DN.