Association of PAI-1 rs1799889 Polymorphism with Susceptibility to Ischemic Stroke: a Huge Meta-Analysis based on 44 Studies

Background: the PAI-1 rs1799889 polymorphism has been reported to be associated with susceptibility to ischemic stroke. However, the results of previous studies have been inconsistent or controversial. Hence, we performed a systematic review and meta-analysis to evaluate the association of PAI-1 rs1799889 polymorphism with ischemic stroke risk. Methods: A comprehensive literature search was performed on PubMed, Web of Science, Scopus, SciELO, CNKI, and CBD databases up to November 05, 2019. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of this association in fixed- or random-effects model. Results: A total of 44 case-control studies with 8,620 cases and 10,260 controls were selected. Pooled data showed a significant association between PAI-1 rs1799889 polymorphism and ischemic stroke risk in the overall populations (GG vs. AA: OR = 0.791, 95% CI 0.633–0.988, p = 0.039; GA vs. AA: OR = 0.807, 95% CI 0.683–0.953, p = 0.012; and GG+GA vs. AA: OR = 0.795, 95% CI 0.637–0.993, p = 0.043). Subgroup analysis by ethnicity revealed a significant association in Asian and Mixed populations, but not in Caucasians. Moreover, stratified analysis by country of origin revealed an increased risk of ischemic stroke in Chinese populations, but not among Dutch (Netherlands) and Swedish. Conclusions: This meta-analysis result suggested that PAI-1 rs1799889 polymorphism was associated with an increased risk of ischemic stroke, especially in Asian and Mixed populations.