Meta-analysis of genome wide association studies (GWAS) on the intolerance of Angiotensin converting enzyme inhibitors

Objectives—To identify SNPs associated with switching from an ACE-inhibitor to an angiotensin receptor blocker (ARB). Methods—Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the GoDARTS study in Scotland. Cases were intolerant subjects who switched from an ACE-inhibitor to an ARB, controls were subjects who used ACE-inhibitors continuously for at least 2 years and did not switch. GWAS using an additive model was run in these sets and results were meta-analysed using GWAMA. Results—972 cases out of 5 161 ACE-inhibitor starters were identified. 8 SNPs within 4 genes reached the GWAS significance level (P<5×10-8) in the meta-analysis (RBFOX3, GABRG2, SH2B1 and MBOAT1). The strongest associated SNP was located in an intron of RBFOX3, which contains a RNA binding protein (rs2061538: MAF=0.16, OR=1.52[95%CI: 1.32-1.76], p=6.2x10-9). Corresponding author: Anke-Hilse Maitland-van der Zee and Colin NA Palmer Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics. Division of Cardiovascular & Diabetes Medicine, Level 5, Mailbox 12 Ninewells Hospital and Medical School, Dundee DD1 9SY, Phone Number: 00441382383155, Fax Number: 00441382668278 c.n.a.palmer@dundee.ac.uk. §*These authors contributed equally to the study. Conflict of interest The authors declare no conflict of interest. Europe PMC Funders Group Author Manuscript Pharmacogenet Genomics. Author manuscript; available in PMC 2017 September 01. Published in final edited form as: Pharmacogenet Genomics. 2017 March ; 27(3): 112–119. doi:10.1097/FPC.0000000000000264. E uope PM C Fuders A uhor M ancripts E uope PM C Fuders A uhor M ancripts Conclusions—These results indicate that genetic variation in abovementioned genes may increase the risk of ACE-inhibitors induced adverse reactions.