The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study.
The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study.
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DOI：
10.1038/jhh.2015.121
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发表时间：
2016-09
影响因子：
2.7
通讯作者：
Irvin MR
中科院分区：
文献类型：
--
作者：
Do AN;Lynch AI;Claas SA;Boerwinkle E;Davis BR;Ford CE;Eckfeldt JH;Tiwari HK;Arnett DK;Irvin MR
非洲裔美国人的高血压患病率是美国最高的。在这一民族中，控制血压对于减少心血管疾病(CVD)相关的发病率和死亡率很重要。已发现遗传变异与BP对治疗的反应有关。以前关于非裔美国人血压治疗反应的药物遗传学研究受到样本量小以及候选基因数量有限的限制，而且往往集中在一种抗高血压治疗上。利用1,131名来自高血压相关遗传学治疗研究的非裔美国人幼稚的参与者，我们在6个月的随访中检查了35个候选基因的变异是否可能调节四种不同降压药的血压反应，包括血管紧张素转换酶抑制剂(赖诺普利)、钙通道阻滞剂(氨氯地平)和α肾上腺素能阻滞剂(多沙唑嗪)与噻嗪利尿剂(氯苯吡酮)。确定了几个与处理互作有关的提示基因。例如，在有两个微小等位基因REN rs6681776的参与者中，服用多沙唑嗪的患者的舒张压反应比服用氯苯磺酮的患者有很大改善(平均−为9.49毫米汞柱，−为1.70毫米汞)(P=0.007)。尽管确定了几个有提示作用的基因座，但经过多次测试校正后，没有一个发现通过了显著标准。考虑到高血压及其后遗症在这一人群中的影响，这项研究强调了遗传因素对血压治疗反应的潜在贡献。需要继续以遗传学为重点的协调一致的研究努力，以改善这一高危群体的治疗反应。
African Americans have the highest prevalence of hypertension in the United States. Blood-pressure control is important to reduce cardiovascular disease (CVD)-related morbidity and mortality in this ethnic group. Genetic variants have been found to be associated with BP response to treatment. Previous pharmacogenetic studies of blood-pressure response to treatment in African Americans suffer limitations of small sample size as well as a limited number of candidate genes, and often focused on one antihypertensive treatment. Using 1,131 African-American treatment naïve participants from the Genetics of Hypertension Associated Treatment (GenHAT) Study, we examined whether variants in 35 candidate genes might modulate blood-pressure response to four different antihypertensive medications, including an angiotensin converting enzyme (ACE) inhibitor (lisinopril), a calcium channel blocker (amlodipine), and an α-adrenergic blocker (doxazosin) as compared to a thiazide diuretic (chlorthalidone) after 6 months of follow-up. Several suggestive gene by treatment interactions were identified. For example, among participants with two minor alleles of REN rs6681776, diastolic blood-pressure response was much improved on doxazosin compared to chlorthalidone (on average −9.49 mmHg vs. −1.70 mmHg) (P=0.007). Although several suggestive loci were identified, none of the findings passed significance criteria after correction for multiple testing. Given the impact of hypertension and its sequelae in this population, this research highlights the potential for genetic factors to contribute to blood-pressure response to treatment. Continued concerted research efforts focused on genetics are needed to improve treatment response in this high risk group.