作者
Christoph Varenhorst, Niclas Eriksson, AASA Johansson, Bryan J Barratt, Emil Hagström, Axel Åkerblom, Ann-Christine Syvänen, Richard C Becker, Stefan K James, Hugo A Katus, Steen Husted, Ph Gabriel Steg, Agneta Siegbahn, Deepak Voora, Renli Teng, Robert F Storey, Lars Wallentin
发表日期
2015/8/1
期刊
European heart journal
卷号
36
期号
29
页码范围
1901-1912
出版商
Oxford University Press
简介
Aims
Ticagrelor, a direct-acting P2Y12-receptor antagonist, is rapidly absorbed and partly metabolized to the major metabolite AR-C124910XX (ARC). To identify single-nucleotide polymorphisms (SNPs) associated with pharmacokinetics of ticagrelor and clinical outcomes, we performed a genome-wide association study (GWAS) in patients treated with ticagrelor in the PLATO trial.
Methods and results
A two-stage design was used for the GWAS with discovery (discovery phase: n = 1812) and replication cohorts (replication phase: n = 1941). The steady-state area under the curve (AUCss) values, estimated by the population pharmacokinetic (PK) models, were log transformed and analysed on a genome-wide scale using linear regression. SNPs were analysed against clinical events using Cox-regression in 4990 patients. An SNP (rs113681054) in SLCO1B1 was associated …
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C Varenhorst, N Eriksson, A Johansson, BJ Barratt… - European heart journal, 2015