Mahmoudpour, SH;
Veluchamy, A;
Siddiqui, MK;
Asselbergs, FW;
Souverein, PC;
de Keyser, CE;
Hofman, A;
... Palmer, CNA; + view all
(2017)
Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors.
Pharmacogenetics and Genomics
, 27
(3)
pp. 112-119.
10.1097/FPC.0000000000000264.
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Abstract
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). Conclusions—These results indicate that genetic variation in abovementioned genes may increase the risk of ACE-inhibitors induced adverse reactions.
| Type: | Article |
|---|---|
| Title: | Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/FPC.0000000000000264 |
| Publisher version: | http://doi.org/10.1097/FPC.0000000000000264 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | ACE inhibitors; ACE-inhibitor intolerance; adverse drug reaction; cough; angioedema; Genome Wide Association Study |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1570836 |
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