Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and risk of venous thromboembolism: A meta-analysis

Introduction

The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism was considered to be associated with risk of venous thromboembolism (VTE), while evidence remains inadequate. To provide a more accurate estimation of this relationship, we performed an updated meta-analysis of all eligible studies.

Materials and Methods

A systematical search was performed in PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure (CNKI) and Cqvip databases to identify relevant studies published before March 6^th 2014. The odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the fixed/random-effects model using Review Manager 5.1 and STATA 12.0.

Results

A total of 34 studies with 3561 cases and 5693 controls were analyzed. Overall, significant association between the PAI-1 4G/5G variant and VTE risk in total population (dominant model: OR = 1.32, 95%CI: 1.13-1.54) was observed. And this variant was also related to the deep vein thrombosis risk (dominant model: OR = 1.60, 95%CI: 1.24-2.06, P = 0.0003). In the subgroup analyses on ethnicity, significant results were obtained in both Asians (dominant model: OR = 2.08, 95%CI: 1.29-3.35, P = 0.003) and Caucasians (dominant model: OR = 1.31, 95%CI: 1.10-1.56, P = 0.003). However, no significant association was found in patients with provoked VTE. In terms of subgroup analyses on co-existence of other thrombotic risk factors, the PAI-1 4G/5G polymorphism was significantly associated with VTE risk in patients with factor V Leiden mutation (dominant model: OR = 1.72, 95%CI: 1.17-2.53), but not in patients with cancer or surgery.

Conclusion

Our findings demonstrate the role of PAI-1 4G/5G polymorphism being a risk candidate locus for VTE susceptibility, especially in patients with other genetic thrombophilic disorders.