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Association of β 2 ‐adrenoreceptor genotypes with bronchodilatory effect of tiotropium in COPD
Author(s) -
UMEDA Nobuaki,
YOSHIKAWA Takahiro,
KANAZAWA Hiroshi,
HIRATA Kazuto,
FUJIMOTO Shigeo
Publication year - 2008
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2008.01259.x
Subject(s) - tiotropium bromide , medicine , copd , bronchodilator , genotype , muscarinic acetylcholine receptor , asthma , bronchodilator agents , quality of life (healthcare) , anesthesia , gastroenterology , endocrinology , receptor , lung , lung function , gene , biochemistry , chemistry , nursing
Background and objective: Recently, there has been interest in interactions of β 2 adrenergic receptors (β 2 ‐AR) and muscarinic acetylcholine receptors (mAChR), which share intracellular signal transduction systems. The aim of the present study was to investigate whether bronchodilator response to tiotropium is influenced by β 2 ‐AR genotype in patients with COPD who show poor responsiveness to inhaled β 2 ‐agonists. Methods: After a 4‐week run‐in period, patients with COPD were treated with inhaled tiotropium bromide (18 μg once daily) for 8 weeks. Spirometric measurements and reversibility testing with inhaled β 2 ‐AR agonists were performed and health‐related quality of life was assessed using the St George's respiratory questionnaire (SGRQ) before and after treatment. Genomic DNA was prepared from peripheral blood and individual genotypes at amino acid 16 of the β 2 ‐AR were examined. Results: Forty‐four patients with COPD completed the study. COPD patients with the Arg/Arg genotype ( n = 22) had a significant increase in FEV 1 during treatment compared with those without the Arg/Arg genotype ( n = 22) (FEV 1 , P = 0.009; FEV 1 %, P = 0.006). While all component and total scores on the SGRQ improved significantly in both genetic groups, changes in impact and total scores were significantly greater in patients with Arg/Arg compared with those without (total scores, P = 0.005; impact scores, P < 0.001). Conclusions: These findings indicate that the homozygous Arg/Arg genotype at amino acid 16 of the β 2 ‐AR could affect bronchodilator response to tiotropium in patients with COPD with significant effects on health‐related quality of life.