Shemirani Amir-Houshang, Antalfi Bálint, Pongrácz Endre, Mezei Zoltán András, Bereczky Zsuzsanna, Csiki Zoltán
aMTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Debrecen bLabPharm Kft, Sátoaljaújhely cDepartment of Pathology, Diósgyori Vasgyári Hospital, Miskolc dDepartment of Neurology, Hetényi Géza Hospital, Szolnok eClinical Research center, University of Debrecen, Medical and Health Science Center fDepartment of Internal medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Blood Coagul Fibrinolysis. 2014 Jun;25(4):364-8. doi: 10.1097/MBC.0000000000000055.
Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.
凝血因子 XIII（FXIII）是纤维蛋白溶解和血凝块硬度的调节剂。其潜在活性 A 亚基（FXIII-A）的 Val34Leu 多态性导致 FXIII 激活更快，影响血凝块结构，并对冠状动脉疾病提供适度保护。少数研究调查了 FXIII-A Val34Leu 多态性对动脉粥样硬化性缺血性卒中（AIS）风险的影响，但结果相互矛盾。在之前的所有研究中，仅纳入了 AIS 存活患者，未探讨性别特异性影响。在这项回顾性多中心队列研究中，我们调查了 FXIII-A Val34Leu 多态性对男性和女性致命性 AIS 风险的影响。对 316 例死于 AIS 的患者，在石蜡包埋组织标本上进行 DNA 分离和基因测定。对人群对照、有 AIS 病史的患者和性别匹配对照，在外周血白细胞提取的基因组 DNA 上进行基因分析。致命性 AIS 患者与其各自对照之间，纯合野生型、杂合基因型、Leu34 携带者和 Leu34 等位基因的患病率无显著差异。以年龄作为协变量的逻辑回归分析表明，在女性中，Leu34 等位基因的纯合表现使 AIS 导致致命结局的风险增加超过三倍。结果表明，FXIII-A Val34Leu 多态性不影响 AIS 的发生，但对其结局的严重程度有影响。这种影响具有性别特异性，在纯合女性中，FXIII-A Val34Leu 多态性的促血栓形成/抗纤维蛋白溶解作用似乎占主导。
