Potential genetic risk factors in angiotensin‐converting enzyme‐inhibitor‐induced angio‐oedema

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Angiotensin‐converting enzyme inhibitor (ACEi)‐induced angio‐oedema is an underestimated clinical life‐threatening problem. • The incidence of this non‐allergic, bradykinin‐induced drug side‐effect is 1 : 4000. • Although most ACEi‐treated patients probably have an increased bradykinin plasma concentration, only 0.5% of them develop an angio‐oedema and nothing is known about potential risk factors. WHAT THIS STUDY ADDS • In our attempt to elucidate the unpredictable character of ACEi‐induced angio‐oedema, we investigated bradykinin B2 receptor 2/3 and c.C181T polymorphisms as well as the ACE insertion/deletion polymorphism in combination with serum ACE activity in 65 patients. • ACE insertion/deletion and bradykinin B2 receptor polymorphisms are not involved in the development of ACEi‐induced angio‐oedema. • Further studies should be carried out to clarify whether a combination of these polymorphisms might be a risk factor for ACEi‐induced angio‐oedema. AIMS The pathophysiology of angiotensin‐converting enzyme inhibitor (ACEi)‐induced angio‐oedema remains unclear. We have investigated the impact of ACE insertion/deletion (I/D) polymorphism in combination with serum ACE activity as well as the bradykinin B2 receptor 2/3 and c.C181T polymorphisms. METHODS We analysed the ACE I/D as well as bradykinin B2 (2/3 and C181T) receptor polymorphisms in 65 patients with documented episodes of ACEi‐induced angio‐oedema and 65 patients matched for age and sex being under ACEi treatment without history of angio‐oedema. Furthermore, we determined serum ACE activity in 47 of the 65 angio‐oedema patients 3 months after the angio‐oedema attack and compared these values with 51 healthy individuals (control II). RESULTS No risk association was identified between ACE I/D (I‐allele: 0.42 vs. 0.41, D‐allele: 0.58 vs. 0.59; P= 0.095) or bradykinin B2 receptor polymorphisms and the development of angio‐oedema during ACEi treatment. We found a trend of lower serum ACE activity in ACE I/I genotypes in comparison with control II (I/I: 28 ± 4.5 vs. 33 ± 1.8 U l−1; ID: 39 ± 3.3 vs. 41 ± 1 U l−1; DD: 56 ± 6.7 vs. 52 ± 1.8 U l−1; P= 0.9). CONCLUSIONS Our data suggest that polymorphism of ACE I/D and the bradykinin B2 receptor polymorphisms are not involved in the development of ACEi‐induced angio‐oedema when considered individually. Further studies should be carried out to clarify whether a combination of these polymorphisms might be a risk factor for ACEi‐induced angio‐oedema.