Pharmacogenetics of ACE inhibitor-induced angioedema and cough: a systematic review and meta-analysis

Aim: Angioedema and cough are the two most important adverse effects of ACE inhibitors (ACEIs). Evidence exists that ACEI-related angioedema/cough is partly genetically determined and several genes have been identified to play a role in the development of ACEI-related adverse effects. Materials & methods: This study was performed in order to evaluate the evidence of these genetic associations and ACEIs' adverse effects. After removing duplicates and critical appraisal, 19 studies were considered to be eligible to review; 14 articles about cough and five articles about angioedema. A separate meta-analysis was performed for the most studied ACE insertion/deletion polymorphism (rs4646994) and its association with cough. Results & conclusion: One gene region (XPNPEP2) was associated with ACEI-induced angioedema in three studies. In our meta-analysis we did not find a significant association between the ACE insertion/deletion polymorphism and ACEI cough.