Frequency of the Factor XIII Val34Leu polymorphism in a Maltese Myocardial Infarction case-control collection

Abstract

Fibrin clot structure is dependent upon the ability of coagulation factor XIII (FXIII) to crosslink fibrin polymers providing resistance to improper activation of chemical, mechanical and enzymatic processes. The F13A1 gene is highly polymorphic and one of the commonest polymorphisms is FXIII Valine34Leucine (FXIII Val34Leu) which is caused by a G to T transition in codon 34 resulting the substitution of valine by leucine in the FXIIIA subunit. FXIII Val34Leu polymorphism accelerates the rate by which thrombin activates FXIII. The influence of FXIII Val34Leu polymorphism on the risk of Myocardial infarction (MI) has not been established yet since inconsistent results have been obtained from different studies. In this study, samples from the Maltese Acute Myocardial Infarction (MAMI) collection were tested for the FXIII Val34Leu (rs5985) using Polymerase Chain reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) using HhaI and electrophoresis. FXIII activity (%) assays were carried out by Prof Lisman as part of an ongoing collaboration. The allele frequencies of the FXIII Val34Leu polymorphisms were 80% (wildtype allele) and 20% (mutant allele). Median FXIII median activity was similar in males and females and also no correlation was found with the different metabolic and environmental factors. The median FXIII activity was almost identical in cases, controls and relatives. However on carrying out stratification based on the FXIII Val34Leu genotype, it was noted that median FXIII activity was markedly higher in individuals possessing the variant Leu allele. The FXIII Val34Leu does not appear to change the risk of MI when the collection was analysed as a whole, but on combining genotype and smoking, it was noted that smokers have an increased risk of MI with increasing number of Leu alleles. Combination of high fibrinogen levels and an increasing number of Leu alleles increase risk of MI in males but not in females.