Association of beta2-adrenoreceptor genotypes with bronchodilatory effect of tiotropium in COPD.
OBJECTIVE
Recently, there has been interest in interactions of beta(2) adrenergic receptors (beta(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 beta(2)-AR genotype in patients with COPD who show poor responsiveness to inhaled beta(2)-agonists.


METHODS
After a 4-week run-in period, patients with COPD were treated with inhaled tiotropium bromide (18 microg once daily) for 8 weeks. Spirometric measurements and reversibility testing with inhaled beta(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 beta(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 beta(2)-AR could affect bronchodilator response to tiotropium in patients with COPD with significant effects on health-related quality of life.
Umeda
Nobuaki
N
Department of Sports Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Yoshikawa
Takahiro
T
Kanazawa
Hiroshi
H
Hirata
Kazuto
K
Fujimoto
Shigeo
S
D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use; D000483:Alleles; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000069447:Tiotropium Bromide
D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D012602:Scopolamine Derivatives; D000420:Albuterol; D000069447:Tiotropium Bromide