β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD

Nobuyuki Hizawa, Hironi Makita, Yasuyuki Nasuhara, Tomoko Betsuyaku, Yoko Itoh, Katsura Nagai, Masaru Hasegawa, Masaharu Nishimura

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background: COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the β2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to β2-agonists; however, the effects of these polymorphisms on responses to β2- agonists in patients with COPD is unknown. Objective: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled β2-agonists in patients with COPD. Design and Participants: A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. Results: The presence of the Arg16 allele was associated with lower BDRs to β2-agonist inhalation. The mean (±SD) log (postbronchodilator FEV1 - prebronchodilator FEV1) values of Gly16 homozygotes (n = 65), Arg16Gly16 heterozygotes n = 106), and Arg16 homozygotes (n = 75) were 2.19 ± 0.43, 2.09 ± 0.42, and 2.01 ± 0.42, respectively (p < 0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p < 0.01). Conclusion: The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting β2-agonists in patients with COPD.

Original languageEnglish
Pages (from-to)1485-1492
Number of pages8
JournalChest
Volume132
Issue number5
DOIs
Publication statusPublished - 2007 Nov
Externally publishedYes

Fingerprint

Bronchodilator Agents
Genetic Polymorphisms
Adrenergic Receptors
Chronic Obstructive Pulmonary Disease
Albuterol
Homozygote
Genotype
Heterozygote
Codon
Haplotypes
Inhalation
Genes
Longitudinal Studies
Cohort Studies
Smoking
Alleles

Keywords

  • β-adrenergic receptor
  • Arg16Gly
  • Bronchodilator response
  • COPD
  • Genetic polymorphism

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Hizawa, N., Makita, H., Nasuhara, Y., Betsuyaku, T., Itoh, Y., Nagai, K., ... Nishimura, M. (2007). β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD. Chest, 132(5), 1485-1492. https://doi.org/10.1378/chest.07-1103

β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD. / Hizawa, Nobuyuki; Makita, Hironi; Nasuhara, Yasuyuki; Betsuyaku, Tomoko; Itoh, Yoko; Nagai, Katsura; Hasegawa, Masaru; Nishimura, Masaharu.

In: Chest, Vol. 132, No. 5, 11.2007, p. 1485-1492.

Research output: Contribution to journalArticle

Hizawa, N, Makita, H, Nasuhara, Y, Betsuyaku, T, Itoh, Y, Nagai, K, Hasegawa, M & Nishimura, M 2007, 'β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD', Chest, vol. 132, no. 5, pp. 1485-1492. https://doi.org/10.1378/chest.07-1103
Hizawa, Nobuyuki ; Makita, Hironi ; Nasuhara, Yasuyuki ; Betsuyaku, Tomoko ; Itoh, Yoko ; Nagai, Katsura ; Hasegawa, Masaru ; Nishimura, Masaharu. / β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD. In: Chest. 2007 ; Vol. 132, No. 5. pp. 1485-1492.
@article{44b9fe93352045fa912e7730d34ff9dd,
title = "β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD",
abstract = "Background: COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the β2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to β2-agonists; however, the effects of these polymorphisms on responses to β2- agonists in patients with COPD is unknown. Objective: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled β2-agonists in patients with COPD. Design and Participants: A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. Results: The presence of the Arg16 allele was associated with lower BDRs to β2-agonist inhalation. The mean (±SD) log (postbronchodilator FEV1 - prebronchodilator FEV1) values of Gly16 homozygotes (n = 65), Arg16Gly16 heterozygotes n = 106), and Arg16 homozygotes (n = 75) were 2.19 ± 0.43, 2.09 ± 0.42, and 2.01 ± 0.42, respectively (p < 0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p < 0.01). Conclusion: The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting β2-agonists in patients with COPD.",
keywords = "β-adrenergic receptor, Arg16Gly, Bronchodilator response, COPD, Genetic polymorphism",
author = "Nobuyuki Hizawa and Hironi Makita and Yasuyuki Nasuhara and Tomoko Betsuyaku and Yoko Itoh and Katsura Nagai and Masaru Hasegawa and Masaharu Nishimura",
year = "2007",
month = "11",
doi = "10.1378/chest.07-1103",
language = "English",
volume = "132",
pages = "1485--1492",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "5",

}

TY - JOUR

T1 - β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD

AU - Hizawa, Nobuyuki

AU - Makita, Hironi

AU - Nasuhara, Yasuyuki

AU - Betsuyaku, Tomoko

AU - Itoh, Yoko

AU - Nagai, Katsura

AU - Hasegawa, Masaru

AU - Nishimura, Masaharu

PY - 2007/11

Y1 - 2007/11

N2 - Background: COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the β2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to β2-agonists; however, the effects of these polymorphisms on responses to β2- agonists in patients with COPD is unknown. Objective: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled β2-agonists in patients with COPD. Design and Participants: A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. Results: The presence of the Arg16 allele was associated with lower BDRs to β2-agonist inhalation. The mean (±SD) log (postbronchodilator FEV1 - prebronchodilator FEV1) values of Gly16 homozygotes (n = 65), Arg16Gly16 heterozygotes n = 106), and Arg16 homozygotes (n = 75) were 2.19 ± 0.43, 2.09 ± 0.42, and 2.01 ± 0.42, respectively (p < 0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p < 0.01). Conclusion: The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting β2-agonists in patients with COPD.

AB - Background: COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the β2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to β2-agonists; however, the effects of these polymorphisms on responses to β2- agonists in patients with COPD is unknown. Objective: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled β2-agonists in patients with COPD. Design and Participants: A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. Results: The presence of the Arg16 allele was associated with lower BDRs to β2-agonist inhalation. The mean (±SD) log (postbronchodilator FEV1 - prebronchodilator FEV1) values of Gly16 homozygotes (n = 65), Arg16Gly16 heterozygotes n = 106), and Arg16 homozygotes (n = 75) were 2.19 ± 0.43, 2.09 ± 0.42, and 2.01 ± 0.42, respectively (p < 0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p < 0.01). Conclusion: The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting β2-agonists in patients with COPD.

KW - β-adrenergic receptor

KW - Arg16Gly

KW - Bronchodilator response

KW - COPD

KW - Genetic polymorphism

UR - http://www.scopus.com/inward/record.url?scp=36349014174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36349014174&partnerID=8YFLogxK

U2 - 10.1378/chest.07-1103

DO - 10.1378/chest.07-1103

M3 - Article

VL - 132

SP - 1485

EP - 1492

JO - Chest

JF - Chest

SN - 0012-3692

IS - 5

ER -