5-Lipoxygenase polymorphism and in-vivo response to leukotriene receptor antagonists.
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.
Fowler
Stephen J
SJ
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
Hall
Ian P
IP
Wilson
Andrew M
AM
Wheatley
Amanda P
AP
Lipworth
Brian J
BJ
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
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