Association of endothelial nitric oxide synthase gene G894T polymorphism with type two diabetes and diabetic nephropathy

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) mediates a large range of processes, and abnormality in the production of NO has been implicated in diabetic complications including diabetic nephropathy (DN). G894T polymorphism in the eNOS gene has been shown to decreased activity the NO levels of plasma. The association between eNOS Glu298Asp gene polymorphism and DN risk is still controversial. The present study investigated the effect of eNOS gene G894T polymorphism on susceptibility to type 2 diabetes (T2D) and DN and measures of kidney function in a population with and without diabetes.

This case-control study was carried out at the diabetes specialist clinic of Golestan Hospital of Ahvaz Jundishapur University of Medical Sciences, Iran, from September 2016 to December 2017. The study comprised 132 patients with T2D (with and without nephropathy). They were compared to 66 normal subjects. The subjects were genotyped for the eNOS G894T polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Blood glucose, HbA1c, BUN, creatinine and urinary albumin were evaluated by a biochemistry analyzer.

Higher prevalence of the mutant T allele and homozygous TT genotypes and biochemical parameters) like FBS, TG, and BUN) were seen in T2D patients compared to healthy subjects. For T2DM, the odds ratios (ORs) for the TT genotype and the T allele carrier were 3.1 (P=0.0001) and 2.6 (P=0.0001), respectively. In contrast to the significant association between the eNOS G894T polymorphism and T2D, we could not find a significant correlation to the DN. For DN, the ORs for the TT genotype and the T allele carrier were 1.1 (P=0.76) and 0.8 (P=0.6). For decreased epidermal growth factor receptor (EGFR) below 60 ml/min/ 1.73 m2 in diabetic patients, the OR for TT was 0.8 (P=0.7).

Our results confirm that the risk of T allele and TT genotype of the eNOS G894T polymorphism were significantly associated with T2D, The TT genotype of this polymorphism also conferred the risk of developing T2D, but they were not correlated with DN and decreased eGFR.