UCSF

Background: In the U.S., Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity and mortality, respectively. Ethnic-specific differences in the response to drug treatment may contribute to differences in disease outcomes. Genetic variants at the beta2 adrenergic receptor (2AR) may modify asthma severity and albuterol responsiveness. We tested the association of 2AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Rican and Mexican asthmatics.

Methods: We used both family-based and cross-sectional tests of association with eight 2AR SNPs in 684 Puerto Rican and Mexican families. Regression analyses were used to determine the interaction between genotype, asthma severity and bronchodilator drug responsiveness.

Results: Among asthmatic Puerto Ricans, the Arg16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.01-0.00001). We found a strong interaction of baseline Forced Expiratory Volume in one second or FEV1 with the Arg16Gly polymorphism in predicting bronchodilator response. Among Puerto Rican asthmatics with baseline FEV1 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Glygenotypes and drug responsiveness among Mexican asthmatics.

Conclusions: Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity and bronchodilator response in asthmatic Puerto Ricans and Mexicans. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness.