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 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.
authors.affiliation: University of California-San Francisco, San Francisco, CA 94143-0833, USA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Choudhry
authors.forename: Ngim
authors.initials: N
authors.lastname: Ung
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Sylvette
authors.initials: S
authors.lastname: Nazario
authors.forename: Jesus
authors.initials: J
authors.lastname: Casal
authors.forename: Alfonso
authors.initials: A
authors.lastname: Torres
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Gorman
authors.forename: Keyan
authors.initials: K
authors.lastname: Salari
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez-Santana
authors.forename: Monica
authors.initials: M
authors.lastname: Toscano
authors.forename: Jody Senter
authors.initials: JS
authors.lastname: Sylvia
authors.forename: MariaElena
authors.initials: M
authors.lastname: Alioto
authors.forename: Richard A
authors.initials: RA
authors.lastname: Castro
authors.forename: Michael
authors.initials: M
authors.lastname: Salazar
authors.forename: Ivan
authors.initials: I
authors.lastname: Gomez
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Fagan
authors.forename: Jorge
authors.initials: J
authors.lastname: Salas
authors.forename: Suzanne
authors.initials: S
authors.lastname: Clark
authors.forename: Craig
authors.initials: C
authors.lastname: Lilly
authors.forename: Henry
authors.initials: H
authors.lastname: Matallana
authors.forename: Moises
authors.initials: M
authors.lastname: Selman
authors.forename: Rocio
authors.initials: R
authors.lastname: Chapela
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Jean G
authors.initials: JG
authors.lastname: Ford
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Drazen
authors.forename: William
authors.initials: W
authors.lastname: Rodriguez-Cintron
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Esteban González
authors.initials: EG
authors.lastname: Burchard
mesh_terms: 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
chemical_list: D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol