与血管紧张素转换酶抑制剂所致咳嗽相关的基因变异：瑞典人群的全基因组关联研究

Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population.

作者信息

Hallberg Pär, Persson Matilda, Axelsson Tomas, Cavalli Marco, Norling Pia, Johansson Hans-Erik, Yue Qun-Ying, Magnusson Patrik Ke, Wadelius Claes, Eriksson Niclas, Wadelius Mia

机构信息

Department of Medical Sciences, Clinical Pharmacology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Department of Medical Sciences, Molecular Medicine & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

出版信息

Pharmacogenomics. 2017 Feb;18(3):201-213. doi: 10.2217/pgs-2016-0184. Epub 2017 Jan 13.

DOI:10.2217/pgs-2016-0184

PMID:28084903

Abstract

AIM

We conducted a genome-wide association study on angiotensin-converting enzyme inhibitor-induced cough and used our dataset to replicate candidate genes identified in previous studies.

PATIENTS & METHODS: A total of 124 patients and 1345 treated controls were genotyped using Illumina arrays. The genome-wide significance level was set to p < 5 × 10.

RESULTS

We identified nearly genome-wide significant associations in CLASP1, PDE11A, KCNMB2, TGFA, SLC38A6 and MMP16. The strongest association was with rs62151109 in CLASP1 (odds ratio: 3.97; p = 9.44 × 10). All top hits except two were located in intronic or noncoding DNA regions. None of the candidate genes were significantly associated in our study.

CONCLUSION

Angiotensin-converting enzyme inhibitor-induced cough is potentially associated with genes that are independent of bradykinin pathways.

摘要

目的

我们对血管紧张素转换酶抑制剂引起的咳嗽进行了全基因组关联研究，并利用我们的数据集对先前研究中确定的候选基因进行了复制。

患者与方法

使用Illumina阵列对总共124例患者和1345例接受治疗的对照进行基因分型。全基因组显著性水平设定为p < 5×10。

结果

我们在CLASP1、PDE11A、KCNMB2、TGFA、SLC38A6和MMP16中发现了接近全基因组显著性的关联。最强的关联是与CLASP1中的rs62151109（优势比：3.97；p = 9.44×10）。除两个基因外，所有顶级命中基因均位于内含子或非编码DNA区域。在我们的研究中，没有候选基因显示出显著关联。