Qian-Qian Yu, Yong Yao, Jing Zhu, Dong-Hong Fu, Tian-Hua Xie, Li Yin, Lan Luan, Jia Cao, Zhe-Yao Gu
Department of Ophthalmology, Affiliated Wuxi People's Hospital of Nanjing Medical University , Wuxi, Jiangsu , China.
Curr Eye Res. 2014 Oct;39(10):1052-8. doi: 10.3109/02713683.2014.894078. Epub 2014 Mar 27.
Imbalance in the production of endothelial nitric oxide synthase (eNOS), which plays an essential role in retinal vascular function, can lead to the development of diabetic retinopathy (DR). To thoroughly address this issue, we performed an updated meta-analysis to evaluate the association between the eNOS 27VNTR (4b/4a) polymorphism and DR in type 2 diabetes mellitus (T2DM).
A search was conducted of PubMed and Chinese language (WanFang) databases through 3 March 2013. Data were retrieved in a systematic manner and analyzed using Stata Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.
Based on the search criteria for DR susceptibility related to the 27VNTR (4b/4a) polymorphism of the eNOS gene, 16 case-control studies (15 articles), comprising 3227 T2DM patients with DR and 3437 T2DM patients without DR, were retrieved. Although no significant associations were uncovered in either the overall analysis or DR subtype groups, a decreased association was detected between the African- (allelic contrast: OR = 0.75, 95% CI = 0.65-0.88) or population-based (PB) studies (dominant genetic model: OR = 0.91, 95% CI = 0.83-0.98) and the eNOS 27VNTR (4b/4a) polymorphism. Stratification according to average duration of DM revealed that T2DM patients with histories of >10 years had an elevated susceptibility to DR compared with those with histories of shorter durations (homozygote comparison: OR = 1.67, 95% CI = 1.09-2.58).
The present meta-analysis suggests that the eNOS 27VNTR (4b/4a) polymorphism potentially decreases the risk of developing DR in T2DM African individuals. The higher degree of susceptibility in patients with longer (>10 years) durations of DM is indicative of the involvement of a gene-environment interaction in determining the risk for DR. Further studies, based on larger sample sizes and additional gene-environment interactions, should be conducted to elucidate the role of eNOS gene polymorphisms, especially 27VNTR (4b/4a), in the risk for DR.
内皮型一氧化氮合酶（eNOS）在视网膜血管功能中起关键作用，其生成失衡可导致糖尿病视网膜病变（DR）的发生。为全面探讨这一问题，我们进行了一项更新的荟萃分析，以评估eNOS 27VNTR（4b/4a）基因多态性与2型糖尿病（T2DM）患者DR之间的关联。
检索截至2013年3月3日的PubMed和中文（万方）数据库。以系统的方式检索数据，并使用Stata统计软件进行分析。采用95%置信区间（CI）的粗比值比（OR）评估关联强度。
根据与eNOS基因27VNTR（4b/4a）多态性相关的DR易感性检索标准，共检索到16项病例对照研究（15篇文章），包括3227例患有DR的T2DM患者和3437例未患DR的T2DM患者。虽然在总体分析或DR亚型组中均未发现显著关联，但在非洲人群（等位基因对比：OR = 0.75，95%CI = 0.65 - 0.88）或基于人群（PB）的研究（显性遗传模型：OR = 0.91，95%CI = 0.83 - 0.98）与eNOS 27VNTR（4b/4a）基因多态性之间检测到关联减弱。根据糖尿病平均病程分层显示，糖尿病病程>10年的T2DM患者与病程较短的患者相比，DR易感性升高（纯合子比较：OR = 1.67，95%CI = 1.09 - 2.58）。
本荟萃分析表明，eNOS 27VNTR（4b/4a）基因多态性可能降低T2DM非洲个体发生DR的风险。糖尿病病程较长（>10年）的患者易感性较高，这表明基因 - 环境相互作用参与了DR风险的决定。应基于更大样本量和更多基因 - 环境相互作用开展进一步研究，以阐明eNOS基因多态性，尤其是27VNTR（4b/4a）在DR风险中的作用。
