Bronić Ana, Ferenčak Goran, Bernat Robert, Leniček-Krleža Jasna, Dumić Jerka, Dabelić Sanja
Sestre Milosrdnice University Hospital Centre, Clinical Institute of Chemistry, Department for Laboratory Diagnostics in Traumatology and Orthopaedics, Zagreb, Croatia.
Medicol Outpatients Clinic, Department of Laboratory Diagnostics, Zagreb, Croatia.
J Med Biochem. 2021 Mar 12;40(2):138-149. doi: 10.5937/jomb0-26839.
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: () A > G in codon 312 of the fibrinogen α-chain gene (rs6050, Thr312AlaFGA), () C > T at position 10034 of the 3 - untranslated region in the fibrinogen γ-chain gene (rs2066865, 10034C > T FGG), () C > T in codon 564 of the FXIII-A subunit gene (rs5982, Pro564LeuFXIII-A), and () C > T in codon 6 of the plasmin inhibitor gene (rs2070863, Arg6TrpPI) in Croatian patients and their association with coronary artery disease (CAD).
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.
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.
Our finding suggests that 10034C > T FGG and Arg6Trp PI are associated with CAD.
在凝血的最后阶段，纤维蛋白原构成框架，而因子 XIII（FXIII）的活性形式负责纤维蛋白纤维和纤溶酶抑制剂（PI）的共价交联，从而有助于凝块稳定。可以预期，凝血因子结构的任何变化都会影响凝血形成并调节动脉粥样硬化血栓形成风险。目的是确定克罗地亚患者中四个单核苷酸多态性的频率：（）纤维蛋白原α链基因密码子312处的A>G（rs6050，Thr312Ala FGA），（）纤维蛋白原γ链基因3'非翻译区第10034位的C>T（rs2066865，10034C>T FGG），（）FXIII-A亚基基因密码子564处的C>T（rs5982，Pro564Leu FXIII-A），以及（）纤溶酶抑制剂基因密码子6处的C>T（rs2070863，Arg6Trp PI）及其与冠状动脉疾病（CAD）的关联。
我们对1,8岁因胸痛和疑似CAD接受冠状动脉造影的连续患者样本进行了非亲属病例对照关联研究。病例为确诊CAD的患者（N=201），对照为无CAD的受试者（N=119）。使用PCR-RFLP分析对样本进行基因分型。
Thr312Ala FGA、10034C>T FGG、Leu564Pro FXIII-A和Arg6Trp PI多态性罕见等位基因的观察频率分别为21%、17%、14%、20%。具有10034C>T FGG CC基因型的患者患CAD的校正比值比具有10034C>T FGG TT基因型的患者高3.5倍（95%CI 1.02-12.03）。具有Arg6Trp PI CC基因型的患者患CAD的比值比具有Arg6Trp PI TT基因型的患者高3.86倍（95%CI 1.23-12.12）。似乎这些与基因型相关的较高比值比也与男性性别相关。在任何其他研究的多态性方面未观察到差异。
我们的发现表明10034C>T FGG和Arg6Trp PI与CAD相关。
