Beta2-adrenoceptor polymorphisms and obstructive airway diseases: important issues of study design.

Abstract:

:1. Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway diseases characterized by airflow obstruction. The beta(2)-adrenoceptor mediates bronchodilatation in response to exogenous and endogenous beta-adrenoceptor agonists. 2. Single nucleotide polymorphisms in the beta(2)-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 beta(2)-adrenoceptor polymorphisms. In contrast, asthma phenotypes, such as asthma severity and bronchial hyperresponsiveness, have been associated with beta(2)-adrenoceptor polymorphisms. Of importance to asthma management, coding region polymorphisms may alter the response to short-acting and long-acting beta-adrenoceptor agonists, which are commonly prescribed asthma treatments. 3. 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 beta(2)-adrenoceptor pharmacogenomics in asthma and COPD.

authors

Yang IA,Ng T,Molenaar P,Fong KM

doi

10.1111/j.1440-1681.2007.04731.x

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

1029-36

issue

10

eissn

0305-1870

issn

1440-1681

pii

CEP4731

journal_volume

34

pub_type

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