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首页> 外文期刊>Pharmacogenetics and genomics >Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment: The GenHAT study
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Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment: The GenHAT study

机译：GenHAT研究显示，基因组可帮助识别随机分组接受降压治疗的人群中冠心病高危和低危的亚组

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OBJECTIVE: To identify panels of genetic variants that predict treatment-related coronary heart disease (CHD) outcomes in hypertensive patients on one of four different classes of initial antihypertensive treatment. The goal was to identify subgroups of individuals on the basis of their genetic profile who benefit most from a particular treatment. METHODS: Candidate genetic variants (n=78) were genotyped in 39 114 participants from Genetics of Hypertension Associated Treatment study, ancillary to Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial. Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial randomized hypertensive participants (≥55 years) to one of four treatments (amlodipine, chlorthalidone, doxazosin, lisinopril). The primary outcome was fatal CHD or nonfatal myocardial infarction (mean follow-up=4.9 years). A pharmacogenetic panel was derived within each of the four treatment groups. Receiver-operating characteristic (ROC) curves estimated the discrimination rate between those with and without a CHD event, on the basis of the addition of the genetic panel risk score. RESULTS: For each treatment group, we identified a panel of genetic variants that collectively improved the prediction of CHD to a small but statistically significant extent. Chlorthalidone (A): NOS3 rs3918226; SELE rs5361; ICAM1 rs1799969; AGT rs5051; GNAS rs7121; ROC comparison, P=0.004; Amlodipine (B): MMP1 rs1799750; Factor5 (F5) rs6025; NPPA rs5065; PDE4D rs6450512; MMP9 rs2274756; ROC comparison, P=0.006; Lisinopril (C): AGT rs5051; PON1 rs705379; MMP12 rs652438; F12 rs1801020; GP1BA rs6065; PDE4D rs27653; ROC comparison, P=0.01; Doxazosin (D): F2 rs1799963; PAI1 rs1799768; MMP7 rs11568818; AGT rs5051; ACE rs4343; MMP2 rs243865; ROC comparison, P=0.007. Each panel was tested for a pharmacogenetic effect; panels A, B, and D showed such evidence (P=0.009, 0.006, and 0.001, respectively) and panel C did not (P=0.09). CONCLUSION: Because each panel was associated with CHD in a specific treatment group but not the others, this research provides evidence that it may be possible to use gene panel scores as a tool to better assess antihypertensive treatment choices to reduce CHD risk in hypertensive individuals.
机译：目的：确定在四种不同类别的初始降压治疗之一中，预测高血压患者治疗相关冠心病（CHD）结果的遗传变异体。目的是根据个体的遗传特征识别出从特定治疗中受益最大的个体亚组。方法：在39114名高血压相关治疗研究的遗传学中对候选基因变异（n = 78）进行了基因分型，该研究是抗高血压和降脂辅助治疗以预防心脏病发作的试验。预防心脏病发作的降压和降脂治疗将高血压参与者（≥55岁）随机分为以下四种治疗方法之一（氨氯地平，氯噻酮，多沙唑嗪，赖诺普利）。主要结果是致命的冠心病或非致命性心肌梗塞（平均随访= 4.9年）。在四个治疗组的每一个中均产生了药理遗传学组。接收者操作特征（ROC）曲线根据遗传专家组风险评分的增加，估算了有无CHD事件者的区分率。结果：对于每个治疗组，我们确定了一组遗传变异，这些变异共同改善了冠心病的预测，但在统计学上意义不大。氯噻酮（A）：NOS3 rs3918226; SELE rs5361; ICAM1 rs1799969; AGT rs5051; GNAS rs7121; ROC比较，P = 0.004;氨氯地平（B）：MMP1 rs1799750;因子5（F5）rs6025; NPPA rs5065; PDE4D rs6450512; MMP9 rs2274756; ROC比较，P = 0.006; Lisinopril（C）：AGT rs5051; PON1 rs705379; MMP12 rs652438; F12 rs1801020; GP1BA rs6065; PDE4D rs27653; ROC比较，P = 0.01;多沙唑嗪（D）：F2 rs1799963; PAI1 rs1799768; MMP7 rs11568818; AGT rs5051; ACE rs4343; MMP2 rs243865; ROC比较，P = 0.007。测试每个组的药物遗传学作用。面板A，B和D显示了这样的证据（分别为P = 0.009、0.006和0.001），面板C没有（P = 0.09）。结论：由于在一个特定的治疗组中每个小组都与冠心病相关，而其他小组则不相关，因此这项研究提供了证据，有可能使用基因组评分作为更好地评估降压治疗选择以降低高血压患者冠心病风险的工具。

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