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Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy.

Authors
Kim, SH; Ye, YM; Lee, HY; Sin, HJ; Park, HS
Citation
Journal of clinical pharmacy and therapeutics, 36(3):399-405, 2011
Journal Title
Journal of clinical pharmacy and therapeutics
ISSN
0269-47271365-2710
Abstract
OBJECTIVE: Inhaled combination therapy composing of long-acting β2-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 AND METHODS: 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 β2-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 β2-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 AND



CONCLUSION: 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.
MeSH terms
Adenylate Cyclase/*geneticsAdministration, InhalationAdrenergic beta-2 Receptor Agonists/administration & dosage/metabolism/*therapeutic useAdultAsthma/*drug therapy/metabolism/physiopathologyBronchodilator Agents/administration & dosage/metabolism/*therapeutic useBudesonide/administration & dosage/metabolism/therapeutic useDrug Therapy, CombinationEthanolamines/administration & dosage/metabolism/therapeutic useFemaleGenetic Association StudiesGlucocorticoids/administration & dosage/metabolism/*therapeutic useHumansLinkage DisequilibriumMaleMiddle Aged*Polymorphism, GeneticReceptors, Adrenergic, beta-2/*geneticsRepublic of KoreaRespiratory System/drug effects/physiopathologyRetrospective StudiesSeverity of Illness Index
DOI
10.1111/j.1365-2710.2010.01196.x
PMID
21545619
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
김, 승현예, 영민박, 해심
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