Factor XIII Val34Leu Polymorphism and the Risk of Myocardial Infarction: A Meta-Analysis.

Abstract

Genetic factors involving blood coagulation are thought to contribute to the pathogenesis of myocardial infarction. A common polymorphism of Factor XIII, Factor XIII Val34Leu, may be protective against developing an acute myocardial infarction, but various studies show conflicting results. We performed a meta-analysis to determine whether the Factor XIII Val34Leu polymorphism is associated with a decreased risk of myocardial infarction. 93 articles were reviewed after a MEDLINE search of the literature (1966 through April Week 1 2005) and 12 case-control studies were selected. We included studies involving patients with objectively diagnosed myocardial infarctions (according to the WHO criteria) provided Factor XIII genotyping data were available. Inclusion decisions, quality assessment and data extraction were conducted by two reviewers. Hardy-Weinberg equilibrium was verified in all studies. Hypothesizing that the Leu allele was protective we performed 3 analyses with the Val/Val genotype as the reference group. Pooled odds ratios and their 95% confidence intervals were determined using the method of DerSimonian-Laird. Prior to pooling, heterogenity testing was performed using the I2 statistic. Funnel plots ruled out the possibility of publication bias. These studies included a total of 8743 patients, of which 3663 were MI patients and 5080 were healthy controls. Using the random effects methods, protective effects were seen with the Leu/Val genotype alone (OR for MI 0.79, 95% CI 0.68–0.93) and with Leu/Val and Leu/Leu genotypes (OR 0.79, 95% CI 0.68–0.93). There was also a protective effect with the Leu/Leu genotype alone, but this was not statistically significant (0.83, 95% CI 0.61–1.12) likley due to the low frequency of this genotype. Removing the first published study (Kohler 1998) due to potential publication bias assocaited with the first study evaluating a genotype did not significantly change the results. Our analysis found that the Factor XIII Leu allele confers a small but significant protective effect against myocardial infarction. The polymorphism may be useful in profiling an individual's susceptibility for arterial thrombosis. It remains to be elucidated whether or not routine testing for the FXIII Val34Leu polymorphism will be clinically relevant.