Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy.
J Clin Pharm Ther
; 36(3): 399-405, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21545619
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
Inhaled combination therapy composing of long-acting ß2-agonist and corticosteroid has been widely applied in the management of asthma, but observed treatment responses vary. The aim of this study was to evaluate the pharmacogenetic effect of the adenylyl cyclase type 9 (ADCY9) gene polymorphism on combination therapy. MATERIALS ANDMETHODS:
Eighty-six mild to moderate Korean asthmatics were enrolled in this clinical trial. After the 2-week 'run-in' period, patients received budesonide (an inhaled corticosteroid) and formoterol (long-acting ß2-agonist) during the following 12-week active treatment period. Forced expiratory volume in 1 s (FEV(1) ) and maximum mid-expiratory flow (MMEF) levels were measured at all visits as primary outcome. ADCY9 (Ile772Met, 150127 C/T, 150130 C/T, 150397 C/T, 150479 C/T, TTTA (5/4) ) and ß2-adrenergic receptor (ADRB2, Arg16Gly) gene polymorphisms were genotyped.RESULTS:
Significant associations were observed between the ADCY9 single nucleotide polymorphisms and percent changes in FEV(1) (Ile772Met T/C, P = 0·030) and MMEF (150397 C/T, P = 0·016) after 8 weeks of combination therapy. Haplotype associations were also observed with respect to percent changes in FEV(1) after 8 weeks of therapy (Ht3[TTCC], P = 0·017). Additive therapeutic effect was observed in those with the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms in terms of percent change in FEV(1) after 8 and 12 weeks of therapy (P = 0·002 and P = 0·027 respectively). WHAT IS NEW ANDCONCLUSION:
Our results suggest that ADCY9 gene polymorphisms may alone, and in combination with ADRB2 gene polymorphisms, contribute to individual response to combination therapy in mild to moderate asthmatics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Asma
/
Broncodilatadores
/
Adenilil Ciclases
/
Receptores Adrenérgicos beta 2
/
Agonistas de Receptores Adrenérgicos beta 2
/
Glucocorticoides
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Clin Pharm Ther
Assunto da revista:
FARMACIA
/
TERAPEUTICA
Ano de publicação:
2011
Tipo de documento:
Article