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

Author:

Hallberg Pär1,Persson Matilda1,Axelsson Tomas2,Cavalli Marco3,Norling Pia4,Johansson Hans-Erik5,Yue Qun-Ying6,Magnusson Patrik KE7,Wadelius Claes3,Eriksson Niclas8,Wadelius Mia1

Affiliation:

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

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

3. Department of Immunology, Genetics & Pathology & Science for Life Laboratory, Uppsala University, Sweden

4. Sickla Health Centre, Nacka, Sweden

5. Department of Public Health & Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden

6. Medical Products Agency, Uppsala, Sweden

7. Swedish Twin Registry, Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm

8. Uppsala Clinical Research Center & Department of Medical Sciences, Uppsala University, Uppsala, Sweden

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 × 10-8. 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 × 10-8). 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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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