与血管紧张素转换酶抑制剂引起的咳嗽相关的变体：一项巢式病例对照全基因组研究。

and variants associated with angiotensin-converting enzyme inhibitor-induced cough: a nested case-control genome-wide study.

机构信息

Department of Pharmacy, Peking University First Hospital, Beijing, 100034, China.

Research Center, Shenzhen Evergreen Medical Institute, Shenzhen, 518057, China.

出版信息

Pharmacogenomics. 2020 Jun;21(9):601-614. doi: 10.2217/pgs-2019-0167. Epub 2020 May 13.

DOI:10.2217/pgs-2019-0167

PMID:32397904

Abstract

We aimed to identify genetic variants associated with ACE inhibitor (ACEI)-induced cough. A nested case-control study was performed among hypertensive Chinese patients receiving enalapril-only therapy. Whole-exome sequencing and genome-wide association analysis were performed. We identified that rs13015243 (odds ratio [OR]: 0.47; 95% CI: 0.34-0.66; p = 7.45 × 10), rs13009649 (OR: 0.48; 95% CI: 0.35-0.67; p = 9.96 × 10) and rs1044147 (OR: 2.67; 95% CI: 1.71-4.17; p = 9.91 × 10) were significantly associated with ACEI-induced cough. Nearly genome-wide significant associations in previously reported candidate risk genes , , , , , or were detected in our dataset. Our results suggest that ACEI-induced cough is associated with noncoding SNPs of and , all of which are independent of the bradykinin pathway. NCT03259399.

摘要

我们旨在鉴定与 ACEI（血管紧张素转化酶抑制剂）诱发咳嗽相关的遗传变异。在接受依那普利单药治疗的高血压中国患者中进行了一项巢式病例对照研究。进行了全外显子组测序和全基因组关联分析。我们发现 rs13015243（比值比 [OR]：0.47；95%CI：0.34-0.66；p=7.45×10）、rs13009649（OR：0.48；95%CI：0.35-0.67；p=9.96×10）和 rs1044147（OR：2.67；95%CI：1.71-4.17；p=9.91×10）与 ACEI 诱发的咳嗽显著相关。在我们的数据集中检测到先前报道的候选风险基因、、、、、、或中的与 ACEI 诱导的咳嗽相关的非编码 SNP 具有近乎全基因组显著关联。我们的结果表明，ACEI 诱发的咳嗽与血管紧张素原和缓激肽 B2 受体的非编码 SNP 相关，所有这些 SNP 均独立于激肽途径。NCT03259399。