β2-ADRENOCEPTOR POLYMORPHISMS AND OBSTRUCTIVE AIRWAY DISEASES: IMPORTANT ISSUES OF STUDY DESIGN

Authors: Yang, Ian A; Ng, Taria; Molenaar, Peter; Fong, Kwun M

Source: Clinical and Experimental Pharmacology and Physiology, Volume 34, Number 10, October 2007 , pp. 1029-1036(8)

Publisher: Blackwell Publishing

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Abstract:

SUMMARY

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Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway diseases characterized by airflow obstruction. The β2-adrenoceptor mediates bronchodilatation in response to exogenous and endogenous β-adrenoceptor agonists.

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Single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2) cause amino acid changes (e.g. Arg16Gly, Gln27Glu) that potentially alter receptor function. Recently, a large cohort study found no association between asthma susceptibility and β2-adrenoceptor polymorphisms. In contrast, asthma phenotypes, such as asthma severity and bronchial hyperresponsiveness, have been associated with β2-adrenoceptor polymorphisms. Of importance to asthma management, coding region polymorphisms may alter the response to short-acting and long-acting β-adrenoceptor agonists, which are commonly prescribed asthma treatments.

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Optimizing study design would enhance the robustness of genetic association studies of ADRB2 polymorphisms in airway diseases. Characteristics of high-quality studies include suitable study design and subject selection, optimal study of polymorphisms and haplotypes, disease outcomes of relevance, adequate sample size, adjustment for confounding factors, supportive functional data and appropriate analysis, interpretation and replication. Enhancing these study design factors will provide high-quality evidence regarding the biological and clinical importance of β2-adrenoceptor pharmacogenomics in asthma and COPD.

Keywords: adrenergic; β2-adrenoceptor/genetics; asthma; genetic; polymorphism; receptors

Document Type: Research article

DOI: 10.1111/j.1440-1681.2007.04731.x

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