Four Genes Reached Genomewide Association Study Significance Level on Intolerance of Angiotensin-Converting Enzyme Inhibitors
The PREDICTION-ADR Consortium conducted a meta-analysis GWAS to identify genetic determinants for Angiotensin-Converting Enzyme (ACE) Inhibitors intolerance in European populations (972 cases and 4189 controls) (PMID: 28030426). ACE inhibitors are commonly used to treat high blood pressure, heart failure and kidney disease. The main reasons for intolerance to the drug are persistent dry cough and life-threatening angio-oedema of the lips, tongue and upper airway. The group identified four genes with eight SNPs reaching genomewide significance (p<5x10-8). These genes are RBFOX3, GABRG2, SH2B1 and MBOAT1. GABRG2 is a member of the GABA-A receptor gene family, and play a major role in the benzodiazepine pathway. The group speculates that GABRG2 could be an interesting target due to the supporting evidence of its role in susceptibility to cough. Unfortunately, the group did not investigate the role of significantly associated genes nor exploring the functional roles of the SNPs within the genes.