Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma.
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.
Choudhry
Shweta
S
University of California-San Francisco, San Francisco, CA 94143-0833, USA.
Ung
Ngim
N
Avila
Pedro C
PC
Ziv
Elad
E
Nazario
Sylvette
S
Casal
Jesus
J
Torres
Alfonso
A
Gorman
Jennifer D
JD
Salari
Keyan
K
Rodriguez-Santana
Jose R
JR
Toscano
Monica
M
Sylvia
Jody Senter
JS
Alioto
MariaElena
M
Castro
Richard A
RA
Salazar
Michael
M
Gomez
Ivan
I
Fagan
Joanne K
JK
Salas
Jorge
J
Clark
Suzanne
S
Lilly
Craig
C
Matallana
Henry
H
Selman
Moises
M
Chapela
Rocio
R
Sheppard
Dean
D
Weiss
Scott T
ST
Ford
Jean G
JG
Boushey
Homer A
HA
Drazen
Jeffrey M
JM
Rodriguez-Cintron
William
W
Silverman
Edwin K
EK
Burchard
Esteban González
EG
D000293:Adolescent; D000420:Albuterol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000483:Alleles; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D001993:Bronchodilator Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008800:Mexico; D020641:Polymorphism, Single Nucleotide; D011647:Puerto Rico / Q000208:ethnology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D012129:Respiratory Function Tests; D014481:United States
D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol