FXIIIB p.H95R and intron K polymorphisms and risk of myocardial infarction in the Maltese

Abstract

The clotting cascade is a natural process that is essential in the occurrence of a vascular injury for the prevention of bleeding. This is however not beneficial when unnecessary clot build-up leads to myocardial infarction (MI), stroke or deep vein thrombosis. For instance, variations present in coagulation factor XIII (FXIII) are thought to influence the factor’s activity, which could ultimately affect the risk of MI. The most common variation studied is FXIIIA p.Val34Leu. Locally, studies of FXIIIB-subunit variants: FXIIIB p.H95R and FXIIIB intron K polymorphism have not yet been carried out. Thus, in this study, these polymorphisms were investigated in samples of the Maltese population obtained from the Maltese Acute Myocardial Infarction (MAMI) study. Genotyping analysis for this study was carried out with a kompetitive allele specific polymerase chain (KASP) reaction assay for FXIIIB p.H95R and a TaqMan assay for FXIIIB intron K. Allele frequency for the FXIIIB intron K was at 87%% for the reference allele and 13% for the alternative allele whilst for FXIIIB p.H95R these were at 91% and 9% respectively. For the median FXIII activity analysis, it was noted that this was similar in males and females as well as in cases, control and relatives. Furthermore, this showed no correlation with the different metabolic and environmental factors analysed. However, stratification for FXIIIB intron K genotypes showed that individuals possessing the alternative allele had a markedly lower FXIII activity level. For FXIIIB p.H95R, there is no significant difference in median FXIII activity between the genotypes. The FXIIIB intron K has a protective effect on MI (ORHom Alt 0.27; 95% CI 0.08-0.98), while FXIIIB p.H95R shows no change in risk of MI (ORHet 1.07 95%CI 0.71-1.61). The protective effect of the intron K variant was lost in individuals in the highest fibrinogen tertile. On combination of both polymorphisms, individuals who were heterozygous and homozygotes alternative for a single polymorphism potentially showed a slight decrease in risk of MI (OR 0.80; 95% CI 0.55-1.17 and OR 0.79; 95%CI 0.51-1.24), whilst a suggestive slight increase was noted for compound heterozygotes (OR 1.45; 95%CI 0.57-3.72).