Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study.
Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study.
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DOI：
10.3390/genes13071260
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发表时间：
2022-07-15
期刊：
影响因子：
3.5
通讯作者：
Irvin, Marguerite R.
中科院分区：
文献类型：
--
作者：
Armstrong, Nicole D.;Srinivasasainagendra, Vinodh;Chekka, Lakshmi Manasa S.;Nguyen, Nam H. K.;Nahid, Noor A.;Jones, Alana C.;Tanner, Rikki M.;Hidalgo, Bertha A.;Limdi, Nita A.;Claas, Steven A.;Gong, Yan;McDonough, Caitrin W.;Cooper-DeHoff, Rhonda M.;Johnson, Julie A.;Tiwari, Hemant K.;Arnett, Donna K.;Irvin, Marguerite R.
高血压是导致心血管疾病死亡的主要危险因素。非裔美国人（AAs）是美国高血压患病率最高的人群，为了减轻该人群的高血压负担，需要更好地控制血压（BP）。先前的研究表明，血压对降压治疗的反应存在相当大的人际差异，这可能与遗传因素有关。利用来自高血压相关治疗遗传学（GenHAT）研究的4297名AA参与者随机分配到氯噻酮组的数据，我们旨在确定与氯噻酮疗效相关的变异。另一个目的是找到导致这些个体空腹血糖（FG）变化的变异。我们对6个月内收缩压和舒张压（SBP和DBP）的变化以及治疗24个月的FG水平进行了全基因组关联分析。我们在国际药物基因组学研究联盟中寻求复制。我们确定了8个与BP反应相关的变异和9个与FG反应相关的变异。一个暗示的LINC02211-CDH9基因间变异被边际复制，具有相同的效应方向。鉴于高血压在AAs中的影响，本研究表明了解氯噻酮治疗期间血压控制和血糖变化的遗传背景可能有助于预防该人群的不良心血管事件。
Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population.
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影响因子：
5.6
作者：
Basson J;Simino J;Rao DC
通讯作者：
Rao DC
Wnt信号传导，一种调节血压的新途径？最新的评论。
影响因子：
5.3
作者：
Abou Ziki MD;Mani A
通讯作者：
Mani A
影响因子：
2.7
作者：
Do AN;Lynch AI;Claas SA;Boerwinkle E;Davis BR;Ford CE;Eckfeldt JH;Tiwari HK;Arnett DK;Irvin MR
通讯作者：
Irvin MR
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
2.1
作者：
Bremer, T;Man, A;Diamond, C
通讯作者：
Diamond, C