Mezei Zoltán A, Bereczky Zsuzsanna, Katona Éva, Gindele Réka, Balogh Emília, Fiatal Szilvia, Balogh László, Czuriga István, Ádány Róza, Édes István, Muszbek László
Division of Clinical Laboratory Science, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei Krt., Debrecen H-4032, Hungary.
Department of Cardiology, Faculty of Medicine, University of Debrecen, 98 Nagyerdei Krt., Debrecen H-4032, Hungary.
Int J Mol Sci. 2015 Jan 6;16(1):1143-59. doi: 10.3390/ijms16011143.
The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.
这项病例对照研究的目的是探讨凝血因子 XIII(FXIII)B 亚基(FXIII-B)基因多态性对冠状动脉疾病风险以及 FXIII 水平的影响。在该研究中,纳入了 687 名因疑似冠状动脉疾病而接受冠状动脉造影的患者以及 994 名代表匈牙利人群的个体。根据显著冠状动脉粥样硬化(CAS)的存在情况和心肌梗死(MI)病史对患者进行分类。对 F13B 基因进行 p.His95Arg 和内含子 K nt29756 C>G 多态性基因分型;后者导致 10 个 C 末端氨基酸被 25 个新氨基酸取代。p.His95Arg 多态性不影响 CAS 或 MI 的风险。在纤维蛋白原水平处于上三分位数的患者中,FXIII-B 内含子 K nt29756 G 等位基因对 CAS 和 MI 具有显著的保护作用。然而,这种效应仅在存在 FXIII-A Leu34 等位基因时才存在,并且揭示了两种多态性之间的协同作用。内含子 K nt29756 G 等位基因的携带者 FXIII 水平显著较低,并且 FXIII 水平处于下三分位数对 MI 具有显著的保护作用。提示联合多态性的保护作用与 FXIII 水平降低有关。