BACKGROUND Renal denervation lowers blood pressure (BP) in patients with uncontrolled hypertension. We conducted an unbiased genomic screen to identify genetic variants that may associate with BP response to renal denervation (RDN). METHODS Patients (n=268) with uncontrolled resistant hypertension (baseline BP, 166±21/90±15 mm Hg) who underwent endovascular RDN using the Symplicity catheter (Medtronic, Inc, Santa Rosa, CA) were included. Reduction in 24-hour ambulatory systolic BP was assessed at 6 months and divided into 2 groups: above and below the median response of 6.0 mm Hg, taking preintervention 24-hour ambulatory BP and regression to the mean into account. Whole exome sequencing assessing 249 669 variants, was conducted using Illumina NovaSeq technology read on a NovaSeq S4 Flow Cell device. RESULTS We did not identify individual gene variants associated with BP response following RDN. These findings were confirmed after adjustment for sex and in a sensitivity analysis looking at tertiles of BP response. We also explored specific variants in AGT, ADD1, ADRB1, ADRB2, and SCNN1A that have been proposed as potential candidate genes for response and found no association (all P>0.13). Gene ontology analysis of variants across the 2 responder groups highlighted differences in biologic processes such as cell adhesion and molecular function such as protein tyrosine kinase activity. CONCLUSIONS The response to RDN, in terms of 24-hour BP reduction, was not associated with the genetic profile of patients with resistant hypertension. These data do not support the use of a genetic score to identify potential responders to RDN.

中文翻译：

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血压对肾去神经支配的反应与遗传变异无关。


背景 肾去神经支配可降低未控制的高血压患者的血压 （BP）。我们进行了无偏倚的基因组筛选，以确定可能与 BP 对肾去神经支配 （RDN） 的反应相关的遗传变异。方法 纳入使用 Symplicity 导管 （Medtronic， Inc， Santa Rosa， CA） 接受血管内 RDN 的未控制的顽固性高血压患者 （n=268） （基线血压，166±21/90±15 mm Hg）。在 6 个月时评估 24 小时动态收缩压的降低情况，并将其分为 2 组：高于和低于 6.0 毫米汞柱的中位反应，考虑干预前 24 小时动态血压和回归平均值。使用 Illumina NovaSeq 技术在 NovaSeq S4 流动槽设备上读取，对 249 669 个变异进行全外显子组测序。结果 我们没有发现与 RDN 后 BP 反应相关的单个基因变异。这些发现在调整性别后和对 BP 反应三分位数的敏感性分析中得到证实。我们还探讨了 AGT 、 ADD1 、 ADRB1 、 ADRB2 和 SCNN1A 中的特异性变异，这些变异已被提议作为潜在的反应候选基因，但未发现关联 （均 P>0.13）。对 2 个反应组的变异进行基因本体分析，突出了生物过程（如细胞粘附）和分子功能（如蛋白酪氨酸激酶活性）的差异。结论 就 24 h 血压降低而言，对 RDN 的反应与顽固性高血压患者的遗传谱无关。这些数据不支持使用遗传评分来识别 RDN 的潜在反应者。