Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Pharmacogenomics J. 2013 Aug;13(4):330-4. doi: 10.1038/tpj.2012.22. Epub 2012 Jun 5.
Nearly one-third of adults in the United States have hypertension, which is associated with increased cardiovascular disease (CVD) morbidity and mortality. The goal of antihypertensive pharmacogenetic research is to enhance understanding of drug response based on the interaction of individual genetic architecture and antihypertensive therapy to improve blood pressure control and ultimately prevent CVD outcomes. In the context of the Genetics of Hypertension Associated Treatment study and using a case-only design, we examined whether single-nucleotide polymorphisms in RYR3 interact with four classes of antihypertensive drugs, particularly the calcium channel blocker amlodipine versus other classes, to modify the risk of coronary heart disease (CHD; fatal CHD and non-fatal myocardial infarction combined) and heart failure (HF) in high-risk hypertensive individuals. RYR3 mediates the mobilization of stored Ca(+2) in cardiac and skeletal muscle to initiate muscle contraction. There was suggestive evidence of pharmacogenetic effects on HF, the strongest of which was for rs877087, with the smallest P-value=0.0005 for the codominant model when comparing amlodipine versus all other treatments. There were no pharmacogenetic effects observed for CHD. The findings reported here for the case-only analysis of the antihypertensive pharmacogenetic effect of RYR3 among 3058 CHD cases and 1940 HF cases show that a hypertensive patient's genetic profile may help predict which medication(s) might better lower CVD risk.
美国近三分之一的成年人患有高血压，这与心血管疾病（CVD）发病率和死亡率的增加有关。抗高血压药物遗传学研究的目标是通过个体遗传结构与抗高血压治疗的相互作用，增强对药物反应的理解，以改善血压控制，最终预防 CVD 结局。在高血压相关治疗的遗传学研究背景下，我们使用仅病例设计，研究了 RYR3 中的单核苷酸多态性是否与四类降压药物（特别是钙通道阻滞剂氨氯地平与其他类别）相互作用，以改变高危高血压个体的冠心病（CHD；致命性 CHD 和非致命性心肌梗死合并）和心力衰竭（HF）的风险。RYR3 介导储存的 Ca（+2）在心脏和骨骼肌中的动员，以启动肌肉收缩。有迹象表明存在 HF 的药物遗传学效应，其中最强的是 rs877087，当比较氨氯地平与所有其他治疗时，共显性模型的最小 P 值=0.0005。对于 CHD 没有观察到药物遗传学效应。在 3058 例 CHD 病例和 1940 例 HF 病例的仅病例分析中，RYR3 的抗高血压药物遗传学效应的报告结果表明，高血压患者的遗传特征可能有助于预测哪种药物可能更好地降低 CVD 风险。
