Background: Increasing attention was focused on the beta2-adrenergic receptor gene (ADRB2), whose genetic variability has been implicated as a risk factor for asthma-related phenotypes. However, only a few studies reported the associations by utilizing haplotypic approaches. We therefore examined the relationship of childhood wheezing illness with polymorphisms at codons 16 and 27, and evaluated the influence of polymorphisms individually and in combination as haplotypes.
Methods: We conducted a genetic case-control study comprising 215 wheezing children and 183 nonwheezing controls, all of whom were selected from 2524 fourth- to ninth-grade schoolchildren in southern Taiwan.
Results: All participants were homozygous at the ADRB2 Thr164 locus. After controlling for possible confounders, ADRB2 Glu27 allele was significantly associated with wheezing illness in all genetic models, but the risks on Arg16Gly genotypes were inconclusive. Estimated frequencies for the three main hyplotypes were Arg16/Gln27 57.2%, Gly16/Gln27 35.3%, Gly16/Glu27 7.4% in wheezing children, and Arg16/Gln27 56.3%, Gly16/Gln27 32.2%, Gly16/Glu27 10.4% in controls. The protective effect of Gly16/Glu27 haplotype remained relative to all other ADRB2 haplotypes [adjusted relative risk (aRR) = 0.58; 95% confidence interval (CI) 0.35-0.97]. As compared with children without Gly16/Glu27 haplotype, those with Gly16/Glu27 haplotype had a significantly lower risk for wheezing illness (aRR = 0.56; 95% CI 0.33-0.99). The copy numbers of Gly16/Glu27 haplotype also showed a clear dose-response relationship on the decreased risks. No significant association was found with the prevalence of wheezing illness for other haplotypes.
Conclusion: We concluded that ADRB2 Glu27 allele and Gly16/Glu27 haplotype were significantly protective factors for wheezing illness in Taiwanese schoolchildren.