ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos

Haig Tcheurekdjian*, Marc Via, Anthony De Giacomo, Harriet Corvol, Celeste Eng, Shannon Thyne, Rocio Chapela, William Rodriguez-Cintron, Jose R. Rodriguez-Santana, Pedro C. Avila, Esteban González Burchard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies. Objective: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A 4 hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. Methods: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. Results: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV1 after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. Conclusion: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma.

Original languageEnglish (US)
Pages (from-to)853-858
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume126
Issue number4
DOIs
StatePublished - Oct 1 2010

Keywords

  • Asthma
  • Latino
  • albuterol
  • association study
  • drug responsiveness
  • genetic polymorphism
  • leukotriene
  • leukotriene modifier

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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