College of Pharmacy, Gachon University, Incheon, Republic of Korea.
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
Ann Acad Med Singap. 2023 Jul 28;52(7):340-347. doi: 10.47102/annals-acadmedsg.202328.
This study aimed to investigate the association between polymorphisms in fibrinogen genes and bleeding risk in patients receiving direct oral anticoagulants (DOACs).
Patients treated with DOACs from June 2018 to December 2021 were enrolled in the study. Genotyping was done for rs2070011, rs6050, and rs2070022 in fibrinogen alpha chain (FGA); rs1800788, rs4220, and rs4463047 in fibrinogen beta chain (FGB); and rs2066865 and rs1800792 in fibrinogen gamma chain (FGG), along with F2 rs5896 and F10 rs5960. Multivariable logistic regression analysis was performed to investigate the risk factors for bleeding and to develop a risk scoring system.
A total of 468 patients were included in the analysis, 14 of whom experienced major bleeding and 36 experienced clinically relevant non-major bleeding. In the multivariable analysis, overdose, anaemia, F2 rs5896, and FGG rs1800792 were found to be significantly associated with bleeding risk. Specifically, patients with the TT genotype of F2 rs5896 and the CC genotype of FGG rs1800792 had 2.1 times (95% confidence interval [CI] 1.1-3.9) and 2.7 times (95% CI 1.2-5.9) higher bleeding risk than the C allele and T allele carriers, respectively. Based on the risk scoring system, patients with 0, 1, 2, 3, 4, and 5 points were predicted to have 5.2%, 10.8%, 22.4%, 32.3%, 42.3%, and 61.8% of bleeding risk, respectively.
To our knowledge, this is the first study to investigate the effects of polymorphisms in fibrinogen genes on DOAC response. After validation, these results will be useful for personalised DOAC therapy.
本研究旨在探讨纤维蛋白原基因多态性与接受直接口服抗凝剂（DOACs）治疗的患者出血风险之间的关系。
本研究纳入了 2018 年 6 月至 2021 年 12 月期间接受 DOAC 治疗的患者。对纤维蛋白原α链（FGA）中的 rs2070011、rs6050 和 rs2070022，纤维蛋白原β链（FGB）中的 rs1800788、rs4220 和 rs4463047，以及纤维蛋白原γ链（FGG）中的 rs2066865 和 rs1800792 进行基因分型，同时对 F2 rs5896 和 F10 rs5960 进行基因分型。采用多变量逻辑回归分析探讨出血的危险因素，并建立风险评分系统。
共纳入 468 例患者，其中 14 例发生大出血，36 例发生临床相关非大出血。多变量分析发现，用药过量、贫血、F2 rs5896 和 FGG rs1800792 与出血风险显著相关。具体来说，F2 rs5896 的 TT 基因型和 FGG rs1800792 的 CC 基因型患者的出血风险分别是 C 等位基因和 T 等位基因携带者的 2.1 倍（95%置信区间 [CI] 1.1-3.9）和 2.7 倍（95%CI 1.2-5.9）。基于风险评分系统，预测 0、1、2、3、4 和 5 分的患者出血风险分别为 5.2%、10.8%、22.4%、32.3%、42.3%和 61.8%。
据我们所知，这是第一项研究纤维蛋白原基因多态性对 DOAC 反应影响的研究。这些结果在经过验证后，将有助于实现 DOAC 的个体化治疗。
