Abstract

Background Recent studies demonstrate that genetic variations in the human β 2-adrenergic receptor (β 2AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain. Objective We determined frequencies of these polymorphisms to explore the association between β 2AR haplotypes and asthma diagnosis and phenotype. Methods This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at β 2AR was identified by polymerase chain reaction–restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between β 2AR haplotype status and asthma diagnosis. Results A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the “Gly16 allele without Glu27” (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). Conclusions Variation in the β 2AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma.

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