Selected genetic polymorphisms in association with diabetic nephropathy in type 2 diabetic patients case control study

Abstract

newlineDiabetic nephropathy is known to be a leading complication of diabetes mellitus, characterized by diverse aspects such as high urinary albumin level, elevated blood pressure, and genetic susceptibility leading to end-stage renal disease. Various genetic association investigations have revealed the link among different genetic variants and increased risk of diabetic nephropathy in type 2 diabetic patients. Amongst them (TGFand#946;1 rs1800471), (PTX3 rs2648875), (PVT1 rs2305619) and (NOS3 rs1799983) newlinewere selected based on their role in the pathway mechanism which leads to the pathogenesis of DN. The aim of the current study was to examine the link of genetic variants such as (TGFand#946;1 rs1800471), (PTX3 rs2648875), (PVT1 rs2305619) and (NOS3 rs1799983) in the progression of DN in diabetic mellitus patients. This case- control study comprised a total of 324 participants, comprising of 108 patients with type 2 diabetic mellitus and DN, 108 type 2 diabetic patients without DN and 108 healthy controls. The samples were genotyped using T-ARMS-PCR and resulted were validated using Sanger sequencing. Statistical analysis proved the link of the genetic polymorphisms and risk of DN by exhibiting high odds ratio with statistical significant results in various genetic models. Amongst the investigated polymorphisms a significant link were indicated between rs1800471 GG+GC genotype (p value=0.0001), rs2305619 G allele (p value=0.005), and rs1799983 T allele (p value=0.002) and high risk of DN in diabetic patients with hypertension. Whereas, the genetic variants like rs2648875 GG+GA genotype (p value=0.0001), and rs1799983 T allele and GT+TT genotype exhibited an elevated risk of DN in diabetic patients with dyslipidemia. A statistically significant difference was found amongst the diabetic patients with and without DN in the levels of clinical parameters, which was observed by the increase of these parameters by the influence of GG genotype of rs1799983 and AG+GG of rs2305619 polymorphisms. In conclusion, the genetic polymorphisms, NOS3 G/T and PTX3 A/G confirm a major influence of their respective genotypes to be significantly concomitant with an enhanced risk of DN in patients with diabetes mellitus. This study can probably assist in identifying the genotypes of the indicated genes in patients with diabetes who have a higher chance to develop diabetic nephropathy at an early stage. This further benefit to alert the highrisk diabetic patients to manage their glycemic control and other causative factors which can avoid or prevent them from progressing to DN. newline