作者
Guillaume Paré, Niclas Eriksson, Thorsten Lehr, Stuart Connolly, John Eikelboom, Michael D Ezekowitz, Tomas Axelsson, Sebastian Haertter, Jonas Oldgren, Paul Reilly, Agneta Siegbahn, Ann-Christine Syvanen, Claes Wadelius, Mia Wadelius, Heike Zimdahl-Gelling, Salim Yusuf, Lars Wallentin
发表日期
2013/4/2
期刊
Circulation
卷号
127
期号
13
页码范围
1404-1412
出版商
Lippincott Williams & Wilkins
简介
Background
Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.
Methods and Results
We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance (P<9×10−8) with a gene-dose effect. Each minor allele …
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G Paré, N Eriksson, T Lehr, S Connolly, J Eikelboom… - Circulation, 2013