Factor XIII B Subunit Polymorphisms and the Risk of Coronary Artery Disease

Abstract

The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

The factor XIII‐A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations

“…Other polymorphisms in FXIII have also been implicated as modifiers of FXIII function, including the FXIII-B intron K c.1952 + 144 C > G polymorphism associated with lower FXIII activity and antigen, which appears to be protective against coronary artery disease only in the presence of both the FXIII-A 34Leu allele and elevated fibrinogen. 38 Thus, although our analysis resolved one aspect of these gene-environment interactions, complete understanding of how these mechanisms operate during thrombus formation in vivo will require further studies.…”

Plasma protein profiling in patients undergoing coronary artery bypass grafting surgery and clinical significance

“…Another protein validated by ELISA in the present study was blood coagulation factor XIII (F13). The main function of F13 is to strengthen fibrin polymers and protect them from the fibrinolysis [ 23 ] and related to protective effect on CAD and myocardial infarction [ 24 ]. However, it was validated by ELISA in the present study and therefore, the role of this protein in CABG patients need to be further investigated.…”

Newly-Recognized Roles of Factor XIII in Thrombosis

“…93 In a Hungarian population, this FXIII-B Ã 3 polymorphism results in lower FXIII activity and antigen levels and is protective against CAD and MI, but only in the presence of both high fibrinogen levels and the FXIII-A Leu34 allele (OR: 0.23, 95% CI: 0.06-0.85 and OR: 0.10, 95% CI: 0.02-0.53, respectively, adjusted for synergy). 92 Together, these studies suggest that incorporating information about these alleles may refine interpretations on the contribution of FXIII to thrombosis in certain populations.…”

“…90 This polymorphism was associated with mildly increased risk of venous thrombosis in Dutch Caucasians (OR: 1.5, 95% CI: 1.1-2.0), 90 but not in Iranians, 91 and is not associated with CAD or MI in a Hungarian population. 92 The FXIII-B Ã 3 polymorphism that predominantly occurs in Asians results in a novel splice acceptor site which replaces the final 10 residues of the C-terminus with 25 new residues containing one additional acidic and two extra basic residues. 93 In a Hungarian population, this FXIII-B Ã 3 polymorphism results in lower FXIII activity and antigen levels and is protective against CAD and MI, but only in the presence of both high fibrinogen levels and the FXIII-A Leu34 allele (OR: 0.23, 95% CI: 0.06-0.85 and OR: 0.10, 95% CI: 0.02-0.53, respectively, adjusted for synergy).…”