Association of plasminogen activator inhibitor-1 4G5G Polymorphism with risk of diabetic nephropathy and retinopathy: a systematic review and meta-analysis

Abstract

Background: The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the findings are conflicting. Herein, we conducted a case-control and meta-analysis study to explore the association of PAI-1 4G5G polymorphism with risk of DNR. Methods: We retrieved PubMed, EMBASE, Web of Knowledge, and CNKI databases and screened eligible studies up to August 15, 2020. The strength of associations was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI). Results: A total of 27 case-control studies including 16 studies with 1,825 cases case and 1,731 controls on DN and eleven studies with 1,397 cases and 1,545 controls on DR were selected. Pooled data showed that the PAI-1 4G5G polymorphism was significantly associated with DN (allele model: OR = 0.674, 95% CI 0.524–0.865, p = 0.002; homozygote model: OR = 0.536, 95% CI 0.351–0.817, p = 0.004; heterozygote model: OR = 0.621, 95% CI 0.427–0.903, p = 0.013; dominant model: OR = 0.575, 95% CI 0.399–0.831, p = 0.003; and recessive model: OR = 0.711, 95% CI 0.515–0.981, p = 0.038) and DR (homozygote model: OR = 0.770, 95% CI 0.621–0.955, p = 0.0.017) risk. Stratified analyses by ethnicity indicated that PAI-1 4G5G polymorphism was associated with DN and DR risk in Asians and Caucasians, respectively. Conclusions: The present meta-analysis revealed that the PAI-1 4G5G polymorphism was associated with increased risk of DN and DR risk. However, well-designed large-scale clinical studies are required to further validate our results.