Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

M Ambroziak,A Kuryłowicz,A Budaj

doi:10.1007/s11239-019-01856-3

Abstract

The aim of the study was to investigate the possible role of coagulation factor XIII (FXIII) plasma activity and its gene (F13A1) Val34Leu variant as well as thrombospondin-2 gene (THBS2) T/G 3′UTR and thrombospondin-4 gene (THBS4) Ala387Pro variants in the development of myocardial infarction (MI) in young patients. The studied group consisted of 158 patients aged < 50 years with MI, and the control groups consisted of 150 healthy people aged < 50 years and 202 patients suffering from MI aged ≥ 50 years. Factor XIII activity was measured by photometric assay; genetic variants were determined using the restriction fragment length polymorphism (RFLP) method. FXIII activity was significantly higher in the young MI group compared with young healthy controls and the MI ≥ 50 group (126.2 U/dl vs. 109.6 U/dl, p < 0.0001; 126.2 U/dl vs. 119.8 U/dl, p = 0.01, respectively). FXIII activity did not correlate with F13A1 gene variants. F13A1, THBS2 and THBS4 genotypes were equally distributed in all studied groups. There was also no statistically significant differences in the prevalence of the extended CC/TT/GG haplotype of F13A1/THBS2/THBS4 variants between the young MI group and the young healthy control group and between the young MI group and the MI aged ≥ 50 group. In conclusion, our study revealed that increased FXIII activity is associated with an increased risk of MI in young patients. None of studied single genetic variants—F13A1 Val34Leu, THBS2 T/G 3′UTR and THBS4 Ala387Pro—and the extended CC/TT/GG haplotype of F13A1/THBS2/THBS4 genes was associated with MI in young age.

Highlights

Atherosclerosis is the result of the interplay between modifiable factors, such as smoking, diet or physical activity, and congenital nonmodifiable factors
factor XIII (FXIII) is a protein consisting of two subunits: subunit A, which has an enzymatic transglutaminase function leading to the thrombus formation, and subunit B, which lacks enzymatic activity but is thought to be a carrier of subunit A and stabilizes FXIII in the circulation [1]
The percentage of patients with increased (> 140 U/dl) FXIII activity was higher in the young myocardial infarction (MI) group (30.8%) compared with the young healthy group (14.7%) and MI ≥ 50 group (18.8%)

Summary

Introduction

Atherosclerosis is the result of the interplay between modifiable factors, such as smoking, diet or physical activity, and congenital nonmodifiable factors. Their joined action, which affects the processes of coagulation, fibrinolysis, lipid metabolism and inflammation, is crucial in the pathogenesis of coronary artery disease (CAD), one of the clinical manifestations of atherosclerosis. One of its most important components is coagulation factor XIII (FXIII). This factor plays a crucial role in the equilibrium between thrombus formation and dissolution. Subunit A is encoded by the F13A1 gene at locus 6p25-p24, and subunit B is encoded by the F13B gene at locus 1q31-q32

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