磺脲类药物与QT、JT及QRS间期的大规模药物基因组学研究：CHARGE药物基因组学工作组
Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.
作者信息
Floyd J S, Sitlani C M, Avery C L, Noordam R, Li X, Smith A V, Gogarten S M, Li J, Broer L, Evans D S, Trompet S, Brody J A, Stewart J D, Eicher J D, Seyerle A A, Roach J, Lange L A, Lin H J, Kors J A, Harris T B, Li-Gao R, Sattar N, Cummings S R, Wiggins K L, Napier M D, Stürmer T, Bis J C, Kerr K F, Uitterlinden A G, Taylor K D, Stott D J, de Mutsert R, Launer L J, Busch E L, Méndez-Giráldez R, Sotoodehnia N, Soliman E Z, Li Y, Duan Q, Rosendaal F R, Slagboom P E, Wilhelmsen K C, Reiner A P, Chen Y-Di, Heckbert S R, Kaplan R C, Rice K M, Jukema J W, Johnson A D, Liu Y, Mook-Kanamori D O, Gudnason V, Wilson J G, Rotter J I, Laurie C C, Psaty B M, Whitsel E A, Cupples L A, Stricker B H
机构信息
Deparments of Epidemiology and Medicine, University of Washington, Seattle, WA, USA.
Department of Medicine, University of Washington, Seattle, WA, USA.
出版信息
Pharmacogenomics J. 2018 Jan;18(1):127-135. doi: 10.1038/tpj.2016.90. Epub 2016 Dec 13.
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.
磺脲类药物是一类常用于治疗2型糖尿病的药物，与心血管疾病风险增加有关。它们对QT间期时长及相关心电图表型的影响是这种不良反应的潜在机制。在11个不同种族的队列中，共有71857名欧洲、非裔美国和西班牙裔/拉丁裔血统个体，这些个体有药物使用和心电图（ECG）测量的重复数据，我们对磺脲类药物使用和三种ECG表型（QT、JT和QRS间期）进行了药物基因组全基因组关联研究。在特定血统的荟萃分析中，8个新的药物基因组位点达到了全基因组显著性阈值（P<5×10），并且先前研究中已与磺脲类药物相关治疗效果及其他药物不良反应相关的CYP2C9中的一个药代动力学变异（rs1057910）得到了重复验证。需要进一步的研究来重复这些新发现并了解其生物学基础。
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