Arginine-16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol

C. N.A. Palmer, B. J. Lipworth (Lead / Corresponding author), S. Lee, T. Ismail, D. F. Macgregor, S. Mukhopadhyay

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    Abstract

    Background: The homozygous presence of the arginine-16 variant of the β2 adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting p2 agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting β2 agonists. Methods: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. Results: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. Conclusions: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

    Original languageEnglish
    Pages (from-to)940-944
    Number of pages5
    JournalThorax
    Volume61
    Issue number11
    Early online date13 Jun 2006
    DOIs
    Publication statusPublished - Nov 2006

    Fingerprint

    Adrenergic Receptors
    Arginine
    Asthma
    Genotype
    Young Adult
    Mouthwashes
    Scotland
    Glycine
    Genes
    Salmeterol Xinafoate
    Down-Regulation
    Cross-Sectional Studies
    Outcome Assessment (Health Care)
    Guidelines
    Interviews
    Pediatrics
    DNA
    Therapeutics

    Cite this

    Palmer, C. N.A. ; Lipworth, B. J. ; Lee, S. ; Ismail, T. ; Macgregor, D. F. ; Mukhopadhyay, S. / Arginine-16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. In: Thorax. 2006 ; Vol. 61, No. 11. pp. 940-944.
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    title = "Arginine-16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol",
    abstract = "Background: The homozygous presence of the arginine-16 variant of the β2 adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting p2 agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting β2 agonists. Methods: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. Results: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95{\%} CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95{\%} CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. Conclusions: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.",
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    Arginine-16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. / Palmer, C. N.A.; Lipworth, B. J. (Lead / Corresponding author); Lee, S.; Ismail, T.; Macgregor, D. F.; Mukhopadhyay, S.

    In: Thorax, Vol. 61, No. 11, 11.2006, p. 940-944.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Arginine-16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol

    AU - Palmer, C. N.A.

    AU - Lipworth, B. J.

    AU - Lee, S.

    AU - Ismail, T.

    AU - Macgregor, D. F.

    AU - Mukhopadhyay, S.

    PY - 2006/11

    Y1 - 2006/11

    N2 - Background: The homozygous presence of the arginine-16 variant of the β2 adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting p2 agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting β2 agonists. Methods: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. Results: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. Conclusions: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

    AB - Background: The homozygous presence of the arginine-16 variant of the β2 adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting p2 agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting β2 agonists. Methods: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. Results: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. Conclusions: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

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    SP - 940

    EP - 944

    JO - Thorax

    JF - Thorax

    SN - 0040-6376

    IS - 11

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