Family-based association analysis of β 2-adrenergic receptor polymorphisms in the childhood asthma management program

Abstract

Background β 2-Adrenergic receptor (B2AR) polymorphisms have been associated with a variety of asthma-related phenotypes, but association results have been inconsistent across different studies. Objective We sought to apply family-based association methods to individual single nucleotide polymorphisms (SNPs) and haplotypes of SNPs in B2AR to define the relationship of these genetic variants to asthma-related phenotypes. Methods DNA samples were obtained from 707 Childhood Asthma Management Program participants, representing 650 sibships, as well as their parents. Genotyping was performed at 8 B2AR SNPs. Qualitative asthma-related phenotypes were analyzed with single SNPs and haplotypes by using TRANSMIT; quantitative asthma-related phenotypes were analyzed with the Family-Based Association Test. Results Several SNPs, including SNP −654 and SNP +46, demonstrated significant associations ( P < .05) to postbronchodilator FEV 1 as both a qualitative (<80% of predicted value) and quantitative phenotype. Quantitative phenotypic association analysis demonstrated significant evidence for association of SNP +523 with bronchodilator responsiveness expressed as a percentage of baseline FEV 1 ( P = .012) or a percentage of predicted FEV 1 ( P = .008). Similar evidence for association between the +523 SNP and qualitative bronchodilator responsiveness phenotypes was also found. Analysis of haplotypes supported an association of B2AR variants with spirometric values and bronchodilator responsiveness. Conclusion B2AR variants are associated with spirometric values and bronchodilator responsiveness, but different regions of the gene provide evidence for association with these phenotypes.