Original article Factor XIII Val34Leu polymorphism as a modulator of fibrin clot permeability and resistance to lysis in patients with severe coronary artery disease

Abstract

Background: A common G to T transition in codon 34 with the subsequent valine with leucine replacement in the factor (F) XIII A-subunit affects fibrin formation and stabilisation in vitro. Data on the effects of Leu34 allele on cardiovascular thromboembolic events in vivo are conflicting.
Aim: We investigated whether FXIII Val34Leu polymorphism is potent enough to affect fibrin clot properties in patients with advanced coronary artery disease (CAD).
Methods: We studied 113 patients, aged 62.8 ± 6.1 years, who were scheduled for elective isolated coronary artery bypass grafting surgery (CABG). Patients were compared with 98 healthy age-matched controls. Ex vivo fibrin clot permeability and lysis time (t50%) were determined in citrated plasma.
Results: Patients scheduled for CABG had lower clot permeability (9.14 ± 1.64 vs. 10.02 ± 1.12 × 10-9 cm²; p = 0.0002) and longer t50% (8.45 ± 1.94 vs. 7.63 ± 1.24 min; p < 0.0001) than controls. The Leu34 carriers, i.e. 9 (8%) Leu34Leu homozygous and 23 (20%) Val34Leu heterozygous subjects, had lower permeability by 23% in the CAD group compared with 81 (72%) patients with Val34Val genotype. A similar intergroup difference was observed for t50% which was longer in Leu34 carriers (p < 0.0001). The FXIII Leu34 allele frequency in the control group was similar as well as the impact of Leu34 allele on fibrin properties. The effect of FXIII Leu34 allele on permeability and t50% was not affected by homocysteine, C-reactive protein and fibrinogen levels in CAD patients and controls.
Conclusions: Like in healthy subjects, in patients scheduled for CABG, the FXIII Leu34 allele is associated with decreased fibrin clot permeability and efficiency of lysis.