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The impact of ABCB1 and CES1 polymorphisms on the safety of dabigatran in patients with non-valvular atrial fibrillation
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  • zhu zhu,
  • Chenyue Qian,
  • Cunjing Su,
  • Hong Tao,
  • Jiaojiao Mao,
  • Zhe Guo,
  • Xinyi Zhu,
  • Jie Pan
zhu zhu

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Chenyue Qian
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Cunjing Su
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Jiaojiao Mao
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Xinyi Zhu
The Second Affiliated Hospital of Soochow University
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Abstract

Aims: 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). Methods: 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. Results: 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). The ABCB1 SNP 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 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. Conclusions: 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.