Background: In 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).
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. 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.
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. It seems that those genotype-related higher odds are also male-gender related. No difference was observed regarding any other investigated polymorphism.
Conclusions: Our finding suggests that 10034C > T FGG and Arg6Trp PI are associated with CAD.
Uvod: U završnoj fazi stvaranja ugruška fibrinogen čini okvir, dok je aktivni oblik faktora XIII (FXIII) odgovoran za kovalentno umrežavanje vlakana fibrina i inhibitora plazmina (PI), doprinoseći tako stabilnosti ugruška. Moglo bi se očekivati da svaka promena strukture faktora koagulacije utiče na stvaranje ugruška i modulira rizik od aterotrom - bota. Cilj je bio da se odredi frekvencija četiri pojedinačna nukleotidna polimorfizma: (I) A > G u kodonu 312 gena a-lanca fibrinogena (rs6050, Thr312AlaFGA), (II) C > T na položaju 10034 3' netransliranog regiona u genu g-lanca fibrinogena (rs2066865, 10034C > TFGG), (III) C > T u kodonu 564 gena podjedinice FXIII-A (rs5982, Pro564LeuFXIII-A), i (IV) C > T u kodonu 6 gena inhibitora plazmina (rs2070863, Arg6TrpPI) kod hrvatskih pacijenata, i njihovu povezanost sa koronarnom arterijskom bolešću (CAD).
Metode: Obavljeno je nepovezano istraživanje slučajeva i kontrola na uzastopnom uzorku pacijenata sa 18 i više godina koji su bili podvrgnuti koronarnoj angiografiji radi ispitivanja bola u grudima i sumnje na CAD. Slučajevi su bili pacijenti sa potvrđenom CAD (N = 201), a kontrolna grupa su bili oni koji nisu imali CAD (N = 119). Genetska konstrukcija uzoraka istražena je pomoću PCR-RFLP analize.
Rezultati: Posmatrane frekvencije retkih alela Thr312Ala FGA, 10034 C > T FGG, Leu564Pro FXIII-A i Arg6Trp PI polimorfizma bile su, redom, 21%, 17%, 14%, 20%. Pacijenti sa 10034 C > T FGG CC genotipom imali su 3,5 puta (95% CI 1,02-12,03) veće prilagođene izglede za dobijanje CAD u odnosu na pacijente sa 10034 C > T FGG TT genotipom. Pacijenti sa Arg6Trp PI CC genotipom imali su 3,86 puta (95% CI 1,23-12,12) veće izglede za CAD u odnosu na pacijente sa Arg6Trp PI TT genotipom. čini se da ti veći izgledi vezani za genotip takođe imaju veze i sa muškim polom. Nije uočena razlika u odnosu na bilo koji drugi istraženi polimorfizam.
Zaključak: Dobijeni rezultati ukazuju na to da su 10034 C > T FGG i Arg6Trp PI povezani sa CAD.
Keywords: FXIII; coronary artery disease; fibrinogen; genotyping; plasmin inhibitor; polymorphisms.
2021 Ana Bronić, Goran Ferenčak, Robert Bernat, Jasna Leniček-Krleža, Jerka Dumić, Sanja Dabelić, published by CEON/CEES.