El-Fattah Amal Ahmed Abd, Sadik Nermin Abdel Hamid, Sedrak Heba, Battah Ahmed, Nabil Mai
Biochemistry department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Internal Medicine department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Gene. 2018 Jan 30;641:212-219. doi: 10.1016/j.gene.2017.10.043. Epub 2017 Oct 17.
Hemostatic genes polymorphisms are well known to be associated with venous thrombosis, but their association with arterial thrombosis especially myocardial infarction (MI) remains to be clarified. We investigated the role of three hemostatic gene polymorphisms, prothrombin G20210A, factor XIII (FXIII) Val34Leu (G/T), and fibrinogen-β-455G/A and their coexistence in Egyptian patients with MI. The possible correlation of these polymorphisms with plasma fibrinogen level was also evaluated. The study included 120 patients with MI and 60 healthy volunteers. Gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. Plasma fibrinogen level was determined by ELISA. Our study showed an increased risk of MI with fibrinogen β-455G/A heterozygosity as well as FXIII Val34Leu homo and heterozygosity. In addition, the FXIII T allele (Leu34) and fibrinogen β-455A allele were significantly associated with MI. Conversely, the prevalence of prothrombin mutation did not differ between patients with MI and controls. Combined carriers of FXIII Leu34 and fibrinogen-β455A alleles were at higher risk of MI, whereas combined FXIII Val34Leu and prothrombin 20210A polymorphisms did not show increased risk for MI compared with controls. Plasma fibrinogen levels were significantly higher in patients with MI than controls. In MI patients, plasma fibrinogen levels were significantly higher in those with FXIII GT/TT or fibrinogen β-455 GA, while were significantly lower in those with prothrombin 20210 GA compared with patients with wild type genotypes. In conclusion, our results suggest a possible thrombotic predisposition of FXIII Val34Leu, fibrinogen β-455G/A polymorphisms and their coexistence for MI. These polymorphisms may add complexity to disease pathology by increasing plasma fibrinogen level. Extended studies are needed to confirm our results; nevertheless, these data may be implicated in genetic counseling and screening of high-risk individuals.
众所周知，止血基因多态性与静脉血栓形成有关，但其与动脉血栓形成尤其是心肌梗死（MI）的关联仍有待阐明。我们研究了三种止血基因多态性，即凝血酶原G20210A、因子 XIII（FXIII）Val34Leu（G/T）和纤维蛋白原-β-455G/A及其共存情况在埃及心肌梗死患者中的作用。还评估了这些多态性与血浆纤维蛋白原水平的可能相关性。该研究纳入了120例心肌梗死患者和60名健康志愿者。使用多重聚合酶链反应和反向杂交技术检测基因多态性。通过酶联免疫吸附测定法测定血浆纤维蛋白原水平。我们的研究表明，纤维蛋白原β-455G/A杂合性以及FXIII Val34Leu纯合性和杂合性会增加心肌梗死风险。此外，FXIII T等位基因（Leu34）和纤维蛋白原β-455A等位基因与心肌梗死显著相关。相反，心肌梗死患者和对照组之间凝血酶原突变的患病率没有差异。FXIII Leu34和纤维蛋白原-β455A等位基因的联合携带者患心肌梗死的风险更高，而与对照组相比，FXIII Val34Leu和凝血酶原20210A多态性的联合并未显示出心肌梗死风险增加。心肌梗死患者的血浆纤维蛋白原水平显著高于对照组。在心肌梗死患者中，FXIII GT/TT或纤维蛋白原β-455 GA患者的血浆纤维蛋白原水平显著更高，而与野生型基因型患者相比，凝血酶原20210 GA患者的血浆纤维蛋白原水平显著更低。总之，我们的结果表明FXIII Val34Leu、纤维蛋白原β-455G/A多态性及其共存可能使心肌梗死具有血栓形成易感性。这些多态性可能通过增加血浆纤维蛋白原水平使疾病病理更加复杂。需要进一步的研究来证实我们的结果；然而，这些数据可能有助于遗传咨询和高危个体的筛查。
