RESUMO
BACKGROUND: In the United States, 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 beta(2)-adrenergic receptor (beta(2)AR) may modify asthma severity and albuterol responsiveness. We tested the association of beta(2)AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Ricans and Mexicans with asthma. METHODS: We used both family-based and cross-sectional tests of association with 8 beta(2)AR single nucleotide polymorphisms 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 Puerto Ricans with asthma, the arginine (Arg) 16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.00001-0.01). We found a strong interaction of baseline FEV(1) with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma with baseline FEV(1) < 80% of predicted, but not in those with FEV(1) > 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma. CONCLUSIONS: Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity, and bronchodilator response in Puerto Ricans and Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness.
Assuntos
Albuterol/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Hispânico ou Latino/genética , Americanos Mexicanos/genética , Adolescente , Albuterol/farmacocinética , Alelos , Asma/genética , Broncodilatadores/farmacocinética , Criança , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , México , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologia , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Análise de Regressão , Testes de Função Respiratória , Estados UnidosRESUMO
In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. To determine whether ethnicity-specific differences in therapeutic response, clinical response, and/or genetic factors contribute to differences in asthma outcomes, we compared asthma-related clinical characteristics among 684 Mexican and Puerto Rican individuals with asthma recruited from San Francisco, New York City, Puerto Rico, and Mexico City. Puerto Ricans with asthma had reduced lung function, greater morbidity, and longer asthma duration than did Mexicans with asthma. Bronchodilator responsiveness, measured as percentage change from baseline FEV1, was significantly lower among Puerto Ricans with asthma than among Mexicans with asthma. Puerto Ricans with asthma had on average 7.3% (95% confidence interval [CI], 4.6 to 9.9; p < 0.001) lower bronchodilator reversibility in FEV1, higher risk of an emergency department visit in the previous year (odds ratio, 2.63; 95% CI, 1.6 to 4.3; p < 0.001), and of previous hospitalization for asthma (odds ratio, 1.94; 95% CI, 1.2 to 3.2; p = 0.009) than Mexicans. Subgroup analysis corroborated that Puerto Ricans with asthma had more severe disease than did Mexicans on the basis of lung function measurements, responsiveness to beta2-adrenergic agonists, and health care use. We conclude that Puerto Ricans with asthma respond less to albuterol than do Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and response to therapy.