Factor XIII Val34Leu Polymorphism Is Protective Against Venous Thromboembolism; a Meta-Analysis.

Controversy over whether the factor XIII Val34Leu polymorphism confers protection against venous thromboembolism (VTE) is a persistent debate in the current thrombosis literature. If an accurate estimate of the protective effect were established, routine screening for this mutation in patients with VTE could provide more precise individual risk-profiling, but presently, it remains undetermined whether it is worthwhile to screen for this polymorphism. We performed a meta-analysis to determine whether the 34Leu allele of the factor XIII gene is associated with a decreased risk of VTE. Studies were identified by searching MEDLINE (1966 through to June Week 2 2004) followed by a manual search of reference lists from previously retrieved articles, symposia proceedings, and abstracts from major thrombosis conferences. Studies were selected for review if they involved unselected objectively diagnosed VTE patients with factor XIII Val34Leu genotypes reported and were a case-controlled study. Inclusion decisions, quality assessment and data extraction were conducted by two reviewers and consensus was achieved by discussion or by a third independent reviewer. Hardy-Weinberg equilibrium of the study control populations were verified. Four of the studies did not report whether they had verified Hardy-Weinberg equilibrium (Balogh, Catto, Margaglione, and Zidane). Authors were contacted for missing data. Forty-five studies were reviewed for eligibility and ten studies met the inclusion criteria. Pooled Odds Ratios and their 95% confidence intervals (CI) were determined using the method of DerSimonian-Laird. Prior to pooling, heterogeneity testing was performed using the Breslow-Day statistic and was insignificant (p = 0.06) which validated testing our FXIII 34Leu recessive model using the random effects model. Funnel plots ruled out the possibility of publication bias. The random effects model gave a combined odds ratio of 0.75 (95% CI= 0.55 to 1.01). Testing our dominant model using a random effects model gave a combined odds ratio of 0.86 (95% CI=0.76 to 0.98). Heterogeneity testing was insignificant (p=0.16). Our meta-analysis found significantly lower odds of VTE with the presence of FXIII 34Leu allele using a dominant model (i.e. the presence of at least one Leu allele). This polymorphism should be given consideration as part of routine risk profiling in patients at risk for VTE.