Genetic variations in the thrombin-activatable fibrinolysis inhibitor gene and risk of cardiovascular disease: a systematic review and meta-analysis.

BACKGROUND:An imbalance between coagulation and fibrinolytic system plays an important role in the pathogenesis of arterial thrombosis. It has been identified that elevated plasma thrombin-activatable fibrinolysis inhibitor (TAFI) concentration, an anti-fibrinolytic factor, is associated with an increased risk of cardiovascular disease (CVD). But the effect of genetic variations in TAFI gene on the risk of CVD is inconclusive. OBJECTIVES:To investigate the associations between two variants Ala147Thr(rs3742264) and Thr325Ile(rs1926447) in TAFI and the risk of CVD. METHODS:Systematic review and meta-analysis of eligible studies published before January 2014. Coronary heart disease(CHD) and stroke are regarded as end-points of CVD. RESULTS:A total of 18 articles including 23 studies were enrolled. Among these articles were 19 studies of Ala147Thr and 15 of Thr325Ile variants, comprising 4,977 CVD patients and 8,082 controls together with 4,890 cases and 8,311 controls, respectively. There were no significant associations between Ala147Thr variant and CVD under allele, dominant, recessive genetic models. Similar results were observed when end-point, ethnicity, sample size, genotyping method were taken into account. Likewise, meta-analysis of Thr325Ile variant did not show significant associations with CVD under three genetic models. Nevertheless, in sub-analysis based on end-point, the TT(Ile/Ile) genotype was associated with a 25% higher risk of coronary heart disease(CHD) (OR=1.25, 95%CI, 1.02-1.54; P=0.03) compared with TC+CC(Thr/Ile+Thr/Thr) genotype(recessive model). CONCLUSIONS:The present meta-analysis failed to confirm the influence of Ala147Thr and Thr325Ile variants on the susceptibility to CVD. However, potentially increased risk of CHD was detected in Ile325 allele carriers under recessive model.