Endothelial Nitric Oxide Synthase Gene Polymorphisms and the Risk of Diabetic Nephropathy in Type 2 Diabetes Mellitus

Abstract

Endothelial dysfunction plays an important role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy (DN). Endothelial nitric oxide synthase (eNOS) gene polymorphisms that affect eNOS activity are associated with endothelial dysfunction. The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients. A total of 400 type 2 diabetic patients were enrolled in this study. The DN group comprised 200 patients; the group of diabetics without nephropathy comprised another 200 patients. Genetic analysis for eNOS gene polymorphisms was done in all subjects. Measurement of nitric oxide levels was estimated. The C allele for -786T>C and the T allele for 894G>T were significantly more frequent in diabetics with nephropathy than in diabetics without nephropathy (p<0.001; odds ratio [OR] and 95% confidence interval [CI] for the C allele=1.64 [1.24-2.17] and p<0.001; OR and 95% CI=1.7 [1.27-2.26] for the T allele). The haplotypes CTa (with all the mutant alleles) and CTb were significantly more common in patients with DN (p=0.01 and 0.003, respectively). These results suggested that the eNOS polymorphisms might represent genetic determinants for developing DN in type 2 diabetic Egyptians.

Associations between endothelial nitric oxide synthase polymorphisms and risk of diabetic nephropathy: an updated meta-analysis

“…Fujita et al 51 and Shimizu et al 45 also found no association between the 4a allele gene and DN in East Asian and Japanese patients, respectively. Moreover, Shoukry 11 showed no significant difference in 4a allele and DN in Egyptian subjects.…”

“…In relation to the eNOS-T786C polymorphism in the promoter region, the C allele has been associated with an increased risk of DN in North Asian Indians 11 and with endstage renal disease (ESRD) in Japanese. 17 However, some studies did not observe an association between this polymorphism and renal insufficiency in Tunisians 14 and in North and South Asian Indians 21 with T2DM.…”

Correlation of Endothelial Nitric Oxide Synthase Gene Polymorphism (GG, TT and GT Genotype) with Proteinuria and Retinopathy in Type 2 Diabetic Patients

“…Angeline in a study on 260 patients showed a correlation between NOS synthase and diabetes mellitus [16]. In a study on 400 diabetic patients, an association between 3 eNOS polymorphism (894G>T, -786T>C, and 27-bp-VNTR) and diabetic nephropathy was found [17]. Ze-jun Ma et al, in a meta-analysis found a significant association between the eNOS-4b/a polymorphism and DN in Chinese population, but not in non-Asian populations [18].…”

Association between Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism and Diabetic Nephropathy Susceptibility

“…Furthermore, the gene polymorphisms of the eNOS 894G>T and À786T>C were also reported to be associated with the developing DN patients. 26 Whether the eNOS Glu298Asp gene polymorphism is just linked with other discrete loci involved in the occurrence of DN is not clear at the moment. Undoubtedly, the limitations mentioned above might affect our final conclusions.…”