title: 5-Lipoxygenase polymorphism and in-vivo response to leukotriene receptor antagonists.
abstract: OBJECTIVE
  To determine whether genetic polymorphisms of the core promoter region of the 5-lipoxygenase gene contribute to the clinical response to leukotriene receptor antagonists.
  
  
  METHODS
  We retrospectively genotyped 52 asthmatics for mutations of this gene from four placebo-controlled studies measuring leukotriene receptor antagonist responses. All studies measured bronchodilator response, and bronchial hyperresponsiveness to adenosine monophosphate was measured in three studies ( n = 34).
  
  
  RESULTS
  Of the 52 patients genotyped, 40 were homozygous wild type, 12 heterozygous, and none was homozygous mutant. There was no significant difference in any improvements conferred by leukotriene receptor antagonists versus placebo in the forced expiratory volume in 1 s (0.20 l for wild-type homozygotes and 0.01 l for heterozygotes), forced mid-expiratory flow rate (0.16 l/s and 0.14 l/s), peak expiratory flow rate (10 l/min and 29 l/min) and adenosine monophosphate 20% fall in forced expiratory volume in 1 s (2.8-fold shift and 2.3-fold shift) between the two genotypes.
  
  
  CONCLUSIONS
  In our population, screening for this polymorphism as an aid to guiding treatment is probably not worthwhile. In addition, we found no difference between homozygous wild types and heterozygotes in terms of bronchodilator response or bronchial hyperresponsiveness with leukotriene receptor antagonists.
authors.affiliation: Asthma and Allergy Research Group, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. b.j.lipworth@dundee.ac.uk
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fowler
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wilson
authors.forename: Amanda P
authors.initials: AP
authors.lastname: Wheatley
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D003521:Cyclopropanes; D005541:Forced Expiratory Volume / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D011110:Polymorphism, Genetic; D011804:Quinolines / Q000627:therapeutic use; D012189:Retrospective Studies; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000627:therapeutic use
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D011804:Quinolines; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; D001094:Arachidonate 5-Lipoxygenase; C093875:montelukast; C062735:zafirlukast