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Published ahead of print on November 19, 2004, doi:10.1164/rccm.200409-1286OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 6, March 2005, 563-570

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Submitted on September 28, 2004
Accepted on November 8, 2004

Pharmacogenetic Differences in Response to Albuterol between Puerto Rican and Mexican Asthmatics

Shweta Choudry1, Ngim Ung1, Pedro C Avila2, Sylvette Nazario3, Jesus Casal3, Alfonso Torres3, Jose R Rodriguez-Santana4, Joanne K Fagan5, Craig Lilly6, Jorge Salas7, Moises Selman7, Rocio Chapela7, Dean Sheppard1, Scott T Weiss6, Jean G Ford8, Homer A Boushey2, Jeffrey M Drazen6, WIlliam Rodriguez-Cintron3, Edwin K Silverman6, and Esteban Gonzalez Burchard1*

1 Department of Medicine, University of California, San Francisco, San Francisco,, CA, USA; Lung Biology Center, San Francisco General Hospital, San Francisco, CA, USA, 2 Department of Medicine, University of California, San Francisco, San Francisco,, CA, USA, 3 Medicine, San Juan VAMC, University of Puerto Rico School of Medicine, San Juan, PR, Puerto Rico, 4 Department of Pediatrics, Pediatric Pulmonary Program of San Juan, San Juan, PR, Puerto Rico, 5 The Harlem Lung Center, Harlem Hospital and Columbia University, New York, NY, USA, 6 Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA, 7 Department of Medicine, Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Distrito Federal, Mexico, 8 The Harlem Lung Center, Harlem Hospital and Columbia University, New York, NY, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: eburch{at}itsa.ucsf.edu.

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 (b2AR) may modify asthma severity and albuterol responsiveness. We tested the association of b2AR 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 {beta}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% of predicted, but not in those with FEV1 > 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 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.
Key words: Pharmacogenetic, b2AR gene, Asthma Genetics, Latinos




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