Association between the valine/leucine(247) polymorphism of beta(2)-glycoprotein I and susceptibility to anti-phospholipid syndrome: a meta-analysis

Abstract

Objective: The objective of this paper is to explore whether the valine/leucine(247) (Val/Leu(247)) polymorphism of beta(2)-glycoprotein I (beta(2)GPI) confers susceptibility to anti-phospholipid syndrome (APS) and thrombosis and predicts positivity for anti-beta(2)GPI antibodies. Methods: A meta-analysis was conducted on the associations between the beta(2)GPI Val/Leu(247) polymorphism and susceptibility to APS and thrombosis and positivity for anti-beta(2)GPI. 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 beta(2)GPI Val/Leu(247) polymorphism showed significant associations between the beta(2)GPI Val allele and APS, thrombosis, and anti-beta(2)GPI 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-beta(2)GPI-positive and -negative patients revealed that the frequency of the Val allele was significantly higher in anti-beta(2)GPI-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 beta(2)GPI 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 beta(2)GPI Val/Leu(247) polymorphism is associated with susceptibility to APS and thrombosis and with anti-beta(2)GPI positivity. Lupus (2012) 21, 865-871.