A number of genes have been identified in diabetic nephropathy. Association between diabetes-associated nephropathy and polymorphisms in the erythropoietin (EPO) gene, variants in the superoxide dismutase 1 (SOD1) gene and plasmacytoma variant translocation 1 (PVT1) gene have been identified. The EPO, SOD1:SFRS15 and PVT1 genes were genotyped using the single nucleotide polymorphism (SNP) technique in 38 diabetic nephropathy patients (Group 1) compared with 64 diabetic type 2 subjects without nephropathy (Group 2) at the Mubarak Alkabeer Hospital, Kuwait. The frequency of the risk allele T of the EPO (rs1617640) gene was high in both groups (0.96 in Group 1 and 0.92 in Group 2). Similarly, SNPs of the PVT1 (rs2720709) gene showed a higher frequency of the risk allele G in both groups (0.70 in the Group 1 and 0.68 in Group 2). Although the frequency of the risk allele A was higher than the frequency of the non-risk allele C of the SOD1:SFRS15 gene in both groups, the lowest probability value was observed in those gene SNPs (P = 0.05). We observed that the A allele of the SOD1:SFRS15 gene (rs17880135) was more frequently present in Group 1 (0.75) compared with Group 2 (0.62). Susceptibility to diabetes-associated nephropathy is partially mediated by genetic predisposition, and screening tests may open the gate for new therapeutic approaches.

ABSTRACT. Diabetic nephropathy is the leading cause of end-stage kidney disease in the world. Many single nucleotide polymorphisms (SNPs) have been associated with diabetic nephropathy. SNPs at the 4.1 protein ezrin, radixin, moesin domain 3 (FRMD3) and cysteinyl t-RNA synthetase (CARS) genes have a well-established relationship with diabetic nephropathy. However, this association has not been evaluated in a Kuwaiti population. DNA was extracted from blood samples obtained from patients with diabetic nephropathy (N = 38); the genes of interest were amplified, and the SNPs were genotypes. Diabetics without nephropathy (N = 64) were used as controls. The risk (G and C) and non-risk (C and T) allele frequencies of the SNPs at the rs1888747 and rs739401 loci of FRMD3 and CARS, respectively, did not differ significantly between the diabetics with (case) and without (control) nephropathy (P > 0.05). These findings suggest that the molecular mechanisms involved in diabetic nephropathy may be different in a Kuwaiti population, compared to other populations (such as Japanese and Caucasian Europeans). The discrepancies observed in our study could also be attributed to the smaller sample size analyzed in this study. Therefore, further analyses with larger samples are required to identify the susceptibility genes in a Middle-Eastern population.