Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis

OBJECTIVE: To conduct a systematic review and updated meta-analysis on the potential association between endothelial nitric oxide synthase (eNOS) 4a/b polymorphism and the risk of developing diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to identify possible clinical biomarkers for early screening of DR. MATERIALS AND METHODS: A meta-analysis based on case-control or cross-sectional studies was conducted to examine the correlation between eNOS 4a/b polymorphism and DR. Pooled odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association strength. RESULTS: We included 19 studies, covering 7838 subjects. An association was observed in Caucasians (allelic model: OR = 1.273, 95% CI: 1.006–1.610, p = .045; recessive model: OR = 0.575, 95% CI: 0.371–0.892, p = .014; dominant model: OR = 1.268, 95% CI: 1.052–1.528, p = .013; homozygote model: OR = 1.833, 95% CI: 1.176–2.856, p = .007). Moreover, population-based studies have indicated an association between eNOS 4a/b polymorphism and DR susceptibility. CONCLUSIONS: The present study showed that intron 4a allele of eNOS 4a/b is a risk factor for DR in Caucasians with T2DM. Thus, eNOS 4a/b may be used as a biomarker for the early screening and diagnosis of DR in Caucasian T2DM patients. KEY MESSAGES: 1. Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with the risk of developing diabetic retinopathy in the overall population, Asians, or Chinese Han patients with type 2 diabetes. However, 4a is a risk factor for the development of diabetic retinopathy in Caucasians. 2. Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with the type of diabetic retinopathy.