Abstract
BackgroundIn the final phase of clot formation, fibrinogen constitutes frame, whereas factor XIII (FXIII) active form is responsible for the covalent cross-linking of fibrin fibres and plasmin inhibitor (PI), thus contributing to clot stability. It could be expected that any change of coagulation factors' structure affects the clot formation and modulates the atherothrombotic risk. The aim was to determine the frequency of four single nucleotide polymorphisms: (i) A > G in codon 312 of the fibrinogen α-chain gene (rs6050, Thr312AlaFGA), (ii) C > T at position 10034 of the 3 - untranslated region in the fibrinogen γ-chain gene (rs2066865, 10034C > T FGG), (iii) C > T in codon 564 of the FXIII-A subunit gene (rs5982, Pro564LeuFXIII-A), and (iv) C > T in codon 6 of the plasmin inhibitor gene (rs2070863, Arg6TrpPI) in Croatian patients and their association with coronary artery disease (CAD).MethodsWe performed the unrelated case-control association study on the consecutive sample of patients 18 years old, who had undergone coronary angiography for investigation of chest pain and suspected CAD. The cases were patients with confirmed CAD (N=201), and the controls were the subjects with no CAD (N=119). Samples were genotyped using PCR-RFLP analysis.ResultsObserved frequencies of the rare alleles of Thr312Ala FGA, 10034C > T FGG, Leu564Pro FXIII-A and Arg6Trp PI polymorphisms were 21%, 17%, 14%, 20%, respectively. Patients with 10034C > T FGG CC genotype had 3.5 times (95% CI 1.02-12.03) higher adjusted odds for CAD than patients with 10034C > T FGG TT genotype. Patients with Arg6Trp PI CC genotype had 3.86 times (95% CI 1.23-12.12) higher odds for CAD than patients with Arg6Trp PI TT genotype. It seems that those genotype-related higher odds are also male-gender related. No difference was observed regarding any other investigated polymorphism.ConclusionsOur finding suggests that 10034C > T FGG and Arg6Trp PI are associated with CAD.
Highlights
Primary causes of death in developed countries are cardiovascular diseases, among which coronary artery disease (CAD) is the most predominant and fatal
Our finding suggests that 10034C > T FGG and Arg6Trp plasmin inhibitor (PI) are associated with CAD
Besides the traditional risk factors, which are well-defined, various genetic variants can represent determinants that influence the individual susceptibility for CAD [1,2,3,4]
Summary
Primary causes of death in developed countries are cardiovascular diseases, among which coronary artery disease (CAD) is the most predominant and fatal. Besides the traditional risk factors, which are well-defined (family history, age, gender, diabetes, cigarette smoking, hypertension, hypercholesterolemia, low HDL cholesterol, hypertriglyceridemia, and obesity), various genetic variants (so far known to a much lesser extent) can represent determinants that influence the individual susceptibility for CAD [1,2,3,4]. CAD is a disease in which stenosis or clot in the coronary blood vessels leads to spectra of clinical phenotypes, among which myocardial infarction (MI) is one of the most dangerous [5, 6], and atherosclerosis or arteriosclerosis is the primary cause of CAD. All the elements involved in the clot formation are important determinants of atherothrombotic risk, and so are fibrinogen and coagulation factor XIII (FXIII) [7,8,9,10]. Fibri(noge)n constitutes cloth frame, whereas the activated form of FXIII (FXIIIa) is responsible for the mechanical strength and cloth stabilisation by covalent cross-linking of fibrin fibres and incorporation of plasmin inhibitor (PI, known as a2-antiplasmin), into the cloth [11,12,13,14,15] (Figure 1)
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