Angioedema: Investigation of genetic and environmental risk factors
The aim of the present research project is to investigate the molecular basis of bradykinin-mediated tissue swellings (angioedema) with a focus on angiotensin converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB) induced angioedema and hereditary angioedema (HAE). Angioedema can become life-threatening events if, e.g., the tongue, larynx or throat are affected. They can appear as a known side effect of ACEi and ARBs. Based on the results of previous research it is assumed that susceptibility to ACEi/ARB-induced angioedema is dependent on a genetic predisposition as well as personal and environmental risk factors. However, the exact biological mechanisms contributing to these angioedema are still largely unknown. Another type of bradykinin-mediated angioedema is HAE which is a rare genetic disease associated with recurrent episodes of tissue swellings. To date, genetic mutations have been identified in four different genes being causal for around 75% of HAE cases. However, in the remaining proportion of patients, the underlying genetic cause is still unknown, which often makes diagnosis and individual therapy difficult or delayed. In addition, not all patients with pathogenic HAE mutations show clinical symptoms. To improve prevention, diagnosis and patient outcome in ACEi/ARB-induced angioedema and HAE, we will use the UK Biobank data and perform state-of-the-art molecular genetic analyses (including genome-wide association and exome sequencing analyses) to (i) identify genetic and non-genetic risk factors for ACEi/ARB-induced angioedema, (ii) assess the frequencies of known monogenic HAE forms within the general population, and (iii) identify potential new candidate genes for HAE. Our results could lead to a better prediction of the occurrence of such angioedema and enable new preventive, diagnostic and therapeutic approaches.