The roles of PAI-1 gene polymorphisms in atherosclerotic diseases: A systematic review and meta-analysis involving 149,908 subjects.

BACKGROUND: The roles of plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in atherosclerotic diseases were intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between PAI-1 genetic variations and atherosclerosis.

METHODS: Eligible studies were searched in PubMed, Medline, Embase and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess relationship between PAI-1 polymorphisms and atherosclerotic diseases.

RESULTS: Ninety-nine studies involving 62,739 cases and 87,169 controls were finally included. Significant associations with the risk of atherosclerosis were detected for the rs2227631 polymorphism in the dominant model (95% CI 0.84-1.00), for the rs1799889 polymorphism in the dominant (95% CI 1.01-1.18), recessive (95% CI 0.90-0.98) and allele (95% CI 1.01-1.12) models. Further subgroup analyses based on type of disease and ethnicity of participants suggested that the rs2227631 polymorphism was significantly associated with the risk of coronary artery disease in the dominant (95% CI 0.71-0.94) and allele (95% CI 0.80-0.94) models, whereas the rs1799889 polymorphism was significantly associated with the risk of myocardial infarction (dominant model: 95% CI 1.09-1.57; recessive model: 95% CI 0.71-0.96; allele model: 95% CI 1.05-1.28) and cerebral infarction (dominant model: 95% CI 1.68-3.51; additive model: 95% CI 0.39-0.77; allele model: 95% CI 1.23-2.00). Moreover, the rs1799889 polymorphism was also significantly correlated with the risk of atherosclerosis in both Asians (dominant model: 95% CI 1.10-1.83; allele model: 95% CI 1.03-1.41) and Caucasians (recessive model: 95% CI 0.87-0.97; allele model: 95% CI 1.01-1.12).

CONCLUSION: In conclusion, our findings indicate that PAI-1 rs2227631 and rs1799889 polymorphisms may serve as genetic biomarkers of atherosclerotic diseases.