Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma

Shweta Choudhry; Ngim Ung; Pedro C. Avila; Elad Ziv; Sylvette Nazario; Jesus Casal; Alfonso Torres; Jennifer D. Gorman; Keyan Salari; Jose R. Rodriguez-Santana; Monica Toscano; Jody Senter Sylvia; Maria Elena Alioto; Richard A. Castro; Michael Salazar; Ivan Gomez; Joanne K. Fagan; Jorge Salas; Suzanne Clark; Craig Lilly; Henry Matallana; Moises Selman; Rocio Chapela; Dean Sheppard; Scott T. Weiss; Jean G. Ford; Homer A. Boushey; Jeffrey M. Drazen; William Rodriguez-Cintron; Edwin K. Silverman; Esteban González Burchard

doi:10.1164/rccm.200409-1286OC

Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma

Shweta Choudhry, Ngim Ung, Pedro C. Avila, Elad Ziv, Sylvette Nazario, Jesus Casal, Alfonso Torres, Jennifer D. Gorman, Keyan Salari, Jose R. Rodriguez-Santana, Monica Toscano, Jody Senter Sylvia, Maria Elena Alioto, Richard A. Castro, Michael Salazar, Ivan Gomez, Joanne K. Fagan, Jorge Salas, Suzanne Clark, Craig LillyHenry Matallana, Moises Selman, Rocio Chapela, Dean Sheppard, Scott T. Weiss, Jean G. Ford, Homer A. Boushey, Jeffrey M. Drazen, William Rodriguez-Cintron, Edwin K. Silverman, Esteban González Burchard^*

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

206 Scopus citations

Abstract

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 β₂- adrenergic receptor (β₂AR) may modify asthma severity and albuterol responsiveness. We tested the association of β₂AR 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 β₂AR 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 FEV₁ with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma 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 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.

Original language	English (US)
Pages (from-to)	563-570
Number of pages	8
Journal	American journal of respiratory and critical care medicine
Volume	171
Issue number	6
DOIs	https://doi.org/10.1164/rccm.200409-1286OC
State	Published - Mar 15 2005

Keywords

Asthma genetics
Latinos
Pharmacogenetic
β-adrenergic receptor gene

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine

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10.1164/rccm.200409-1286OC

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Choudhry, S., Ung, N., Avila, P. C., Ziv, E., Nazario, S., Casal, J., Torres, A., Gorman, J. D., Salari, K., Rodriguez-Santana, J. R., Toscano, M., Sylvia, J. S., Alioto, M. E., Castro, R. A., Salazar, M., Gomez, I., Fagan, J. K., Salas, J., Clark, S., ... Burchard, E. G. (2005). Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. American journal of respiratory and critical care medicine, 171(6), 563-570. https://doi.org/10.1164/rccm.200409-1286OC

@article{7b20d10769b8465390d0ea853f3b6479,

title = "Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma",

abstract = "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 β2- adrenergic receptor (β2AR) may modify asthma severity and albuterol responsiveness. We tested the association of β2AR 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 β2AR 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 FEV1 with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma 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 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.",

keywords = "Asthma genetics, Latinos, Pharmacogenetic, β-adrenergic receptor gene",

author = "Shweta Choudhry and Ngim Ung and Avila, {Pedro C.} and Elad Ziv and Sylvette Nazario and Jesus Casal and Alfonso Torres and Gorman, {Jennifer D.} and Keyan Salari and Rodriguez-Santana, {Jose R.} and Monica Toscano and Sylvia, {Jody Senter} and Alioto, {Maria Elena} and Castro, {Richard A.} and Michael Salazar and Ivan Gomez and Fagan, {Joanne K.} and Jorge Salas and Suzanne Clark and Craig Lilly and Henry Matallana and Moises Selman and Rocio Chapela and Dean Sheppard and Weiss, {Scott T.} and Ford, {Jean G.} and Boushey, {Homer A.} and Drazen, {Jeffrey M.} and William Rodriguez-Cintron and Silverman, {Edwin K.} and Burchard, {Esteban Gonz{\'a}lez}",

year = "2005",

month = mar,

day = "15",

doi = "10.1164/rccm.200409-1286OC",

language = "English (US)",

volume = "171",

pages = "563--570",

journal = "American Review of Respiratory Disease",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "6",

}

Choudhry, S, Ung, N, Avila, PC, Ziv, E, Nazario, S, Casal, J, Torres, A, Gorman, JD, Salari, K, Rodriguez-Santana, JR, Toscano, M, Sylvia, JS, Alioto, ME, Castro, RA, Salazar, M, Gomez, I, Fagan, JK, Salas, J, Clark, S, Lilly, C, Matallana, H, Selman, M, Chapela, R, Sheppard, D, Weiss, ST, Ford, JG, Boushey, HA, Drazen, JM, Rodriguez-Cintron, W, Silverman, EK & Burchard, EG 2005, 'Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma', American journal of respiratory and critical care medicine, vol. 171, no. 6, pp. 563-570. https://doi.org/10.1164/rccm.200409-1286OC

TY - JOUR

T1 - Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma

AU - Choudhry, Shweta

AU - Ung, Ngim

AU - Avila, Pedro C.

AU - Ziv, Elad

AU - Nazario, Sylvette

AU - Casal, Jesus

AU - Torres, Alfonso

AU - Gorman, Jennifer D.

AU - Salari, Keyan

AU - Rodriguez-Santana, Jose R.

AU - Toscano, Monica

AU - Sylvia, Jody Senter

AU - Alioto, Maria Elena

AU - Castro, Richard A.

AU - Salazar, Michael

AU - Gomez, Ivan

AU - Fagan, Joanne K.

AU - Salas, Jorge

AU - Clark, Suzanne

AU - Lilly, Craig

AU - Matallana, Henry

AU - Selman, Moises

AU - Chapela, Rocio

AU - Sheppard, Dean

AU - Weiss, Scott T.

AU - Ford, Jean G.

AU - Boushey, Homer A.

AU - Drazen, Jeffrey M.

AU - Rodriguez-Cintron, William

AU - Silverman, Edwin K.

AU - Burchard, Esteban González

PY - 2005/3/15

Y1 - 2005/3/15

N2 - 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 β2- adrenergic receptor (β2AR) may modify asthma severity and albuterol responsiveness. We tested the association of β2AR 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 β2AR 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 FEV1 with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma 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 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.

AB - 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 β2- adrenergic receptor (β2AR) may modify asthma severity and albuterol responsiveness. We tested the association of β2AR 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 β2AR 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 FEV1 with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma 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 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.

KW - Asthma genetics

KW - Latinos

KW - Pharmacogenetic

KW - β-adrenergic receptor gene

UR - http://www.scopus.com/inward/record.url?scp=20144363204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144363204&partnerID=8YFLogxK

U2 - 10.1164/rccm.200409-1286OC

DO - 10.1164/rccm.200409-1286OC

M3 - Article

C2 - 15557128

AN - SCOPUS:20144363204

SN - 1073-449X

VL - 171

SP - 563

EP - 570

JO - American Review of Respiratory Disease

JF - American Review of Respiratory Disease

IS - 6

ER -

Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma

Abstract

Keywords

ASJC Scopus subject areas

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