[The role of beta 2-adrenoceptor gene polymorphisms in asthma].
It has been reported that beta 2-adrenoceptor polymorphisms at nucleotide 46 (Arg16 to Gly) and nucleotide 79 (Gln27 to Glu) enhance and suppress receptor downregulation after prolonged exposure to a beta 2-agonist in vitro, respectively. To elucidate the role of these polymorphisms in bronchial asthma, the author studied the following three points: (1) the prevalence of these polymorphisms in the Japanese population, (2) whether these polymorphisms influence the clinical characteristics of asthma and (3) whether Arg16 to Gly polymorphism causes changes in baseline airway tone, methacholine airway responsiveness, and bronchoprotective and non-pulmonary effects of a beta 2-agonist after 2 weeks of regular, inhaled beta 2-agonist therapy in mild and moderate asthmatic patients. The allele frequencies of Gly16 and Glu27 in the Japanese healthy population were 0.49 and 0.09, respectively; both were significantly lower than those of Caucasians. The percentage of the Gly16/Gly genotype was significantly higher in moderate to severe asthma than in mild asthma (14.0 and 33.3%, respectively, p < 0.05). After regular inhaled salbutamol, a significant decrease of FEV1 (p < 0.05) and a significant increase of airway responsiveness (p < 0.02) were observed in the patients with Gly16/Gly. Although there were no significant changes in the bronchoprotective effect of salbutamol among the three genotypes, the increase in plasma cAMP induced by inhaled salbutamol was significantly attenuated in the patients with Gly16/Gly (p < 0.05). These results suggest a racial difference in the prevalence of beta 2-adrenoceptor polymorphisms that may be important modifiers of clinical characteristics of bronchial asthma.
Sato
R
R
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000627:therapeutic use; D000403:Airway Resistance; D000420:Albuterol / Q000009:adverse effects / Q000627:therapeutic use; D044466:Asian People; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D015536:Down-Regulation; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D007564:Japan; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D044465:White People
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol