Association between the valine/leucine247 polymorphism of β2-glycoprotein I and susceptibility to anti-phospholipid syndrome: a meta-analysis

Abstract

Objective: The objective of this paper is to explore whether the valine/leucine247 (Val/Leu247) polymorphism of β2-glycoprotein I (β2GPI) confers susceptibility to anti-phospholipid syndrome (APS) and thrombosis and predicts positivity for anti-β2GPI antibodies. Methods: A meta-analysis was conducted on the associations between the β2GPI Val/Leu247 polymorphism and susceptibility to APS and thrombosis and positivity for anti-β2GPI. Results: A total of 1507 patients with APS and 1450 controls in 12 comparative studies were included in this meta-analysis. Meta-analysis of the β2GPI Val/Leu247 polymorphism showed significant associations between the β2GPI Val allele and APS, thrombosis, and anti-β2GPI positivity (odds ratio (OR) 1.316, 95% confidence interval (CI) 1.068–1.621, p = 0.010; OR 1.908, 95% CI 1.195–3.046, p = 0.007; OR 1.630, 95% CI 1.018–2.609, p = 0.042, respectively). A direct comparison between anti-β2GPI-positive and -negative patients revealed that the frequency of the Val allele was significantly higher in anti-β2GPI-positive patents (OR 1.514, 95% CI 1.017–1.253, p = 0.041). Furthermore, a direct comparison between thrombosis-positive and -negative patients also indicated that the Val/Val + Val/Leu and the Val/Val vs. Leu/Leu genotypes of the β2GPI polymorphism were significantly elevated in patients with thrombosis (OR 2.817, 95% CI 1.200–6.610, p = 0.017; OR 3.312, 95% CI 1.338–8.200, p = 0.010, respectively). Conclusion: This meta-analysis shows that the β2GPI Val/Leu247 polymorphism is associated with susceptibility to APS and thrombosis and with anti-β2GPI positivity.