Association of beta(2)-adrenoreceptor variants with bronchial hyperresponsiveness

Because of its involvement in the regulation of airway tone, the beta(2)-ad renoreceptor is considered a candidate for bronchial hyperresponsiveness (B HR) associated with asthma. This notion is supported by several reports tha t have implicated the chromosomal region 5q31-q33 harboring the gene for th e beta(2)-adrenoreceptor in the genetics of asthma and related phenotypes. We performed a population-based association study focusing on BHR as a qual itative trait and omitting other asthma-related phenotypes. From a German p opulation sample of 1,150 individuals we extracted all 152 bronchohyperreac tive probands, who were compared with 295 bronchonormoreactive control subj ects. All individuals were genotyped for three single nucleotide polymorphi sms of the beta(2)-adrenoreceptor gene resulting in variants at the amino a cid positions 16, 27, and 164. The genotyping protocol used allowed the det ermination of haplotypes of these polymorphisms. Whereas no individual poly morphism was associated with BHR, the Gly16/Gln27/Th164 haplotype was signi ficantly underrepresented in the case group indicating a protective effect of this haplotype with regard to BHR. Upon reanalysis by sex a significant association persisted only for female probands.