Department of Pharmacy, The Second Affiliated Hospital of Soochow University, 215004, Suzhou, Jiangsu, China.
Department of cardiology, The Second Affiliated Hospital of Soochow University, 215004, Suzhou, Jiangsu, China.
BMC Cardiovasc Disord. 2022 Nov 11;22(1):481. doi: 10.1186/s12872-022-02910-4.
This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF).
We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up.
Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events.
Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.
本研究旨在分析非瓣膜性心房颤动（NVAF）患者中达比加群的遗传变异与血浆浓度及临床结局之间的关系。
我们进行了一项前瞻性研究，纳入了在真实世界中接受达比加群治疗的 NVAF 患者。共招募了 86 例接受 110mg DE 每日两次治疗的患者进行本研究。从每位患者采集血样，进行基因分型和达比加群血浆浓度测定。在 1.5 年的随访期间记录所有出血和血栓栓塞并发症。
83 例患者在达比加群的谷血浆水平时提供了样本，58 例患者在达比加群的峰血浆水平时提供了样本。CES1 SNP rs8192935 与达比加群的谷血浆浓度有显著相关性（P=0.013）。我们的结果表明，中国人群中 CES1 SNP rs8192935 显著影响达比加群的谷血浆浓度，与非携带者相比，G 等位基因携带者的达比加群谷血浆浓度增加。ABCB1 SNP c.2482-2236G>A（rs4148738）与附加模型中的大出血事件相关（P=0.046，OR=3.29）和显性模型（P=0.040，OR=8.17）。此外，ABCB1 SNP c.3435 C>T（rs1045642）与附加模型中的大出血事件发生率相关（P=0.043，OR=3.34）和显性模型（P=0.046，OR=7.77）。然而，所有 SNP 与轻微出血事件的发生率均无显著相关性。
我们的结果表明，CES1 多态性 rs8192935 与达比加群的谷血浆浓度相关。与非携带者相比，G 等位基因携带者的达比加群谷血浆浓度增加。ABCB1 多态性 rs4148738 和 rs1045642 首次在中国人群中与大出血事件的风险增加相关。
