title: Association between a 27-bp variable number of tandem repeat polymorphism in intron 4 of the eNOS gene and risk for diabetic retinopathy Type 2 diabetes mellitus: a meta-analysis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Affiliated Wuxi People's Hospital of Nanjing Medical University , Wuxi, Jiangsu , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qian-Qian
authors.forename: Yao
authors.initials: Y
authors.lastname: Yong
authors.forename: Zhu
authors.initials: Z
authors.lastname: Jing
authors.forename: Fu
authors.initials: F
authors.lastname: Dong-Hong
authors.forename: Xie
authors.initials: X
authors.lastname: Tian-Hua
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Luan
authors.initials: L
authors.lastname: Lan
authors.forename: Cao
authors.initials: C
authors.lastname: Jia
authors.forename: Gu
authors.initials: G
authors.lastname: Zhe-Yao
mesh_terms: D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: 27VNTR (4b/4a); decreased risk; diabetic retinopathy; enos; meta-analysis type 2 diabetes mellitus; polymorphism