title: Role of interactions in pharmacogenetic studies: leukotrienes in asthma.
abstract: Researchers have identified thousands of loci involved in complex traits and drug response. However, in most cases they only explain a small proportion of the heritability of the trait. Among different strategies conducted to identify this 'missing heritability', here we illustrate the importance of complex gene-environment interactions using findings regarding the role of leukotrienes on the bronchodilator response to albuterol in Latino asthmatics. Patients managing their asthma with leukotriene-modifying medication presented higher increases in the bronchodilator response to albuterol. Moreover, interactions between genes responsible for leukotriene production were associated with a decreased risk of asthma. Combining genetic and pharmacologic effects, leukotriene-modifying users carrying certain combinations of alleles presented higher improvements in lung function after bronchodilator administration. Genes and drugs act at different orders of interaction (from individual effects to gene-gene-drug-drug interactions) and population-specific effects have to be considered. These results may be extrapolated to other complex phenotypes.
authors.affiliation: Department of Psychiatry & Clinical Psychobiology, University of Barcelona, 08035 Barcelona, Spain. mvia@ub.edu
authors.forename: Marc
authors.initials: M
authors.lastname: Via
authors.forename: Haig
authors.initials: H
authors.lastname: Tcheurekdjian
authors.forename: Esteban
authors.initials: E
authors.lastname: González Burchard
mesh_terms: D000420:Albuterol / Q000008:administration & dosage; D000483:Alleles; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D054316:Biomarkers, Pharmacological; D001993:Bronchodilator Agents / Q000008:administration & dosage; D059647:Gene-Environment Interaction; D030342:Genetic Diseases, Inborn / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage; D015289:Leukotrienes / Q000235:genetics / Q000627:therapeutic use*; D017058:Mexican Americans / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods*; D010641:Phenotype
chemical_list: D054316:Biomarkers, Pharmacological; D001993:Bronchodilator Agents; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D000420:Albuterol