Association of fibrinogen and plasmin inhibitor, but not coagulation factor XIII gene polymorphisms with coronary artery disease

Abstract

Background: In the final phase of cloth formation, fibri(noge)n constitutes frame whereas factor XIII (FXIII) active form is responsible for the covalent cross-linking of fibrin fibers 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 modulate 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, Thr312Ala FGA), (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, Pro564Leu FXIII-A), and (iv) C>T in codon 6 of the plasmin inhibitor gene (rs2070863, Arg6Trp PI) in Croatian patients and their association with coronary artery disease (CAD).
 Methods: We 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. Cases were patients with confirmed CAD (N=201) and controls were the subjects with no CAD (N=119). Samples were genotyped using PCR-RFLP analysis.
 Results: Observed 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. No difference was observed regarding any other investigated polymorphism,
 Conclusion: Our finding suggests that 10034C>T FGG and Arg6Trp PI are associated with CAD.

Susceptibility of MMP3 gene polymorphism to coronary artery disease: A meta-analysis

“…In over-dominant genetic model, MMP3 -1612 5A/6A was a risk factor for CAD. Inconsistent with our findings, a relevant study reported that morbid risk and progression risk are higher in subjects carrying MMP3 -1612 6A homozygous than those carrying MMP3 -1612 5A homozygous [32] . Xu et al [33] suggested that MMP3 and MMP9 mutations could be utilized as hallmarks for predicting susceptibility to CAD.…”

Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics

“…Specifically, Met-α2AP (Arg6) was cleaved about eight times more rapidly than Met-α2AP (Trp6) [36]. Recently, Bronic et al have shown in a Croatian cohort that individuals with Arg6Trp α2AP CC genotype had an almost 4-fold higher risk of coronary artery disease compared with Arg6Trp α2AP TT genotype [37].…”

Plasmin Inhibitor in Health and Diabetes: Role of the Protein as a Therapeutic Target

“…However, no such protection was observed against coronary artery disease (CAD) and myocardial infarction (MI). In a recent study on the potential association of the polymorphism (pR6W, rs2070863) with CAD and MI, Bronic and colleagues reported that patients with R6W PI CC genotype had 3.86 times higher odds ratio of risk factor for the CAD than the patients with R6W PI TT genotype in a group of Croatian patients [45].…”