title: Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis.
abstract: BACKGROUND
  Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes.
  
  
  METHODS
  Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.
  
  
  RESULTS
  Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57).
  
  
  CONCLUSIONS
  The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene-environment interaction in determining the risk of diabetic retinopathy.
authors.affiliation: Tianjin Medical University, 22 Qixiangtai Road, Tianjin, 300020, PR China.
authors.forename: Tengyue
authors.initials: T
authors.lastname: Zhang
authors.forename: Chong
authors.initials: C
authors.lastname: Pang
authors.forename: Ningdong
authors.initials: N
authors.lastname: Li
authors.forename: Elaine
authors.initials: E
authors.lastname: Zhou
authors.forename: Kanxing
authors.initials: K
authors.lastname: Zhao
mesh_terms: D048909:Diabetes Complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005006:Ethnicity; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D018570:Risk Assessment
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human