Association of allelic variants of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase with thrombosis or ocular involvement in Behcet's disease: A systematic review and meta-analysis

Thrombosis is frequent in patients with Behcet's disease (BD), although the exact cause remains uncertain. Some single nucleotide polymorphism (SNP) (G1691A in factor V gene, also called factor V Leiden [FVL], G20210A in prothrombin gene and C677T in methyltetrahydrofolate reductase [MTHFR] gene) have been associated with thrombosis and ocular involvement in BD with controversial results. Aim: To assess the effects of FVL, prothrombin and MTHFR SNP variants in patients with BD and thrombosis and ocular involvement by means of a systematic review and meta-analysis. Methods: We retrieved studies analyzing the genotype of the above-mentioned polymorphism among patients with BD. A meta-analysis was conducted in a random effects model and calculations of odds ratio (OR) and confidence intervals (CI) were done. Sensitivity analysis and tests for heterogeneity of the results were performed. Results: 27 previous studies analyzed the association of BD and thrombosis with the FVL, prothrombin and MTHFR polymorphisms. A significant association was found between the possession of the AA or GA genotypes of FVL polymorphism among patients with BD and the presence of any thrombosis (OR= 2.51; 95% CI: 1.68, 3.74; P<0.00001). In addition, a significant association was found between the possession of the GA or AA genotypes and the presence of BD (OR= 2.67; 95% CI: 1.93. 3.72; P<0.00001) when cases with BD and healthy controls were compared. This association was not found when studies from Turkey were excluded. No association was found between prothrombin and MTHFR SNPs and thrombosis in BD, and no association between any SNP and ocular involvement was shown either. Conclusions: Factor V Leiden could be responsible for some thrombotic events in at least Turkish patients. However, this relationship has to be demonstrated from a pathogenic point of view. (C) 2013 Elsevier B.V. All rights reserved.