Association between eNOS 4b/a Polymorphism and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: A Meta-Analysis

Abstract

Many studies have assessed the association between eNOS-4b/a polymorphism and the risk of diabetic retinopathy (DR) among type 2 diabetic subjects. However, the results are inconsistent. In order to derive a more precise estimation of the association, a meta-analysis was conducted. Fifteen studies with 3, 183 cases and 3, 410 controls were enrolled by searching the databases of Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The main analysis indicated no significant association between eNOS-4b/a polymorphism and the risk of DR in overall population [allelic model: OR = 0.94 (0.79–1.11); additive model: OR = 0.91 (0.73–1.14); recessive model: OR = 1.01 (0.81–1.25); dominant model: OR = 0.91 (0.75–1.09)]. Subgroup analysis by ethnicity also indicated no significant association. In conclusion, the current meta-analysis did not observe any association between the polymorphism of eNOS 4b/a and the risk of DR among type 2 diabetic subjects. However, larger well-designed studies are required to confirm this finding.

The joint effect of the endothelin receptor B gene (EDNRB) polymorphism rs10507875 and nitric oxide synthase 3 gene (NOS3) polymorphism rs869109213 in Slovenian patients with type 2 diabetes mellitus and diabetic retinopathy

“…Since it was characterized in the mid-1990s, many polymorphic sites have been described in the human NOS3 gene, including the selected VNTR. However, previous studies on the association between rs869109213 and the risk for DR among T2DM patients reported conflicting and inconclusive results, which might be due to interethnic differences in the distribution of NOS3 polymorphisms [14,19]. Here we confirmed an association between the 4a4a homozygotes of rs869109213 and the occurrence of DR in Slovenian (Caucasians) patients with T2DM.…”

“…Several other authors reported the association between the NOS3 rs869109213 and DR in Caucasians with T2DM [19,21]. For example, Cheema et al [21] found that the 4a4a genotype of rs869109213 was an independent protective factor for DR and was associated with a low risk of DR.…”

Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population

“…The NOS3 gene is located on chromosome 7q 35–36, and has 26 exons that span more than 21 kb of the genome . In recent years, the human NOS3 gene has been considered as a candidate gene for mediating the susceptibility to T2DM, and the association of several NOS3 genetic polymorphisms (such as rs1799983, a 27‐bp repeat in intron 4, and rs2070744) with the susceptibility to T2DM have been assessed . In our present research, NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model.…”

Polymorphic variations in manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) genes contribute to the development of type 2 diabetes mellitus in the Chinese Han population

“…The eNOS gene is located on chromosome 7q35-36 and includes 26 exons, spanning 21 kb (Ma et al, 2014b). Nitric oxide (NO) is produced as a result of the oxidation of L-arginine by eNOS (Moncada and Higgs, 1993).…”

“…Elevated ROS production and reduced NO bioavailability, together with the intermediate product peroxynitrite, significantly account for apoptosis in the endothelial cells, and endothelial dysfunction in T2DM (Johansen et al, 2005). The presence of polymorphisms in eNOS might contribute to a decrease in eNOS activity, reduction in the NO level, and has been reported as a potential factor affecting the pathogenesis and development of T2DM (Ma et al, 2014b).…”