ET B receptor polymorphism is associated with airway obstruction

<p>Abstract</p> <p>Background</p> <p>Endothelin-1 (EDN1) has been involved in the development of airway obstruction and inflammation in asthma. Several polymorphisms have been identified among the genes encoding for preproET1, an inactive precursor of ET-1, and for ET_A(EDNRA) and ET_B(EDNRB), the two receptors for EDN1. In the present work, we hypothesised that molecular variation in these genes could be a major determinant of the degree of bronchial obstruction. The purpose of this study was to investigate whether the genetic polymorphisms of <it>preproET-1</it>, <it>EDNRA </it>and <it>EDNRB </it>genes were associated with the degree of airway obstruction, assessed by FEV₁.</p> <p>Methods</p> <p>Polymorphisms of <it>preproET-1, EDNRA and EDN</it>RB were first studied in a population of adult asthmatic patients. Results were confirmed in a large population of adults from the general population from the ECRHS II study.</p> <p>Results</p> <p>In our population of adult asthmatic patients, the EDNRB-30G>A (Leu277Leu) polymorphism (GG genotype) is strongly associated with a low FEV₁and with a higher percentage of patients with FEV1 < 80% of predicted value. No relationship was found between pulmonary function and EDNRA-1363C>T (His323His) or preproET-1-595G>T (Lys198Asp) polymorphism. In the adult population from the ECRHS II, we found a similar association between GG genotype and a low FEV₁or a higher percentage of subjects with FEV1 < 80% predicted, especially in the subgroups of asthmatics subjects (OR = 4.31 (95%CI 1.03 – 18.04)) and smokers (OR = 7.42 (95%CI 1.69 – 32.6)).</p> <p>Conclusion</p> <p>the EDNRB-30G>A polymorphism could be a determinant of airway obstruction in humans with predisposing factors such as tobacco smoke exposure or asthma.</p>

Abstract licence: CC BY-NC-ND

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