ETB receptor polymorphism is associated with airway obstruction.
BACKGROUND
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 ETA (EDNRA) and ETB (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 preproET-1, EDNRA and EDNRB genes were associated with the degree of airway obstruction, assessed by FEV1.


METHODS
Polymorphisms of preproET-1, EDNRA and EDNRB 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.


RESULTS
In our population of adult asthmatic patients, the EDNRB-30G>A (Leu277Leu) polymorphism (GG genotype) is strongly associated with a low FEV1 and 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 FEV1 or 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)).


CONCLUSIONS
the EDNRB-30G>A polymorphism could be a determinant of airway obstruction in humans with predisposing factors such as tobacco smoke exposure or asthma.
Taillé
Camille
C
Service de Pneumologie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France. camille.taille@bch.aphp.fr
Guénégou
Armelle
A
Almolki
Abdelhamid
A
Piperaud
Marie
M
Leynaert
Bénédicte
B
Vuillaumier
Sandrine
S
Neukirch
Françoise
F
Boczkowski
Jorge
J
Aubier
Michel
M
Benessiano
Joëlle
J
Crestani
Bruno
B
D000328:Adult; D017677:Age Distribution; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015897:Comorbidity; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D044023:Receptor, Endothelin B / Q000235:genetics*; D017678:Sex Distribution; D012907:Smoking / Q000453:epidemiology
D044023:Receptor, Endothelin B