Polymorphisms in the beta(2)-adrenoreceptor gene are associated with decreased airway responsiveness

Background There are a number of candidate genes thought to play a role in the development of asthma. Polymorphisms at amino acid positions 16 (argini ne to glycine) and 27 (glutamine to glutamic acid) of the Pz-adrenoreceptor (B2AR) gene are known to be functionally relevant and have been associated with more severe forms of asthma, nocturnal asthma and decreased airway re sponsiveness in asthmatic subjects. Objective To determine if these polymorphisms contribute to the development of asthma by investigating the associations between the polymorphisms at a mino acid positions 16 and 27 of the B2AR gene and asthma-related parameter s in a large, phenotypically well-characterized population which was unsele cted for asthma. Methods Subjects (n = 332) were characterized using physiological assessmen ts, immunological data and information obtained from questionnaire. PCR was used to generate a 229 base pair fragment spanning the mutations of intere st. Genotype was determined using allele-specific oligonucleotide hybridiza tion and confirmed in 10% of the samples by direct sequencing. Multivariate analysis of the association between genotype and phenotype was then undert aken. Results Homozygotes for Glu27 were significantly less responsive to histami ne than Gln27 homozygotes. In addition, Arg16 homozygotes were more likely to 'wheeze during a cold', in comparison with Gly16 homozygotes. However, t here was no association between either polymorphism and physician-diagnosed asthma, eczema, skin reactivity to common allergens or total and specific serum IgE levels. The two polymorphisms were found to be in significant lin kage disequilibrium. Conclusion The polymorphism at position 27 was associated with decreased ai rway responsiveness in the study population and the polymorphism at positio n 16 was associated with increased wheeze during respiratory infection, but neither was associated with physician-diagnosed asthma or any of the other variables considered.