ALOX5 promoter genotype and response to montelukast in moderate persistent asthma

Respir Med. 2008 Jun;102(6):857-61. doi: 10.1016/j.rmed.2008.01.011. Epub 2008 Mar 12.

Abstract

Background: It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported.

Methods: Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5).

Results: Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment.

Conclusions: It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients. The genetic study could identify those patients most likely to respond to montelukast.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / therapeutic use*
  • Adolescent
  • Adult
  • Age Distribution
  • Anti-Asthmatic Agents / therapeutic use*
  • Arachidonate 5-Lipoxygenase / genetics*
  • Asthma / drug therapy
  • Asthma / genetics*
  • Asthma / physiopathology
  • Cyclopropanes
  • Female
  • Forced Expiratory Volume
  • Genotype
  • Humans
  • Immunoglobulin E / blood
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics*
  • Quinolines / therapeutic use*
  • Sex Distribution
  • Sulfides
  • Tandem Repeat Sequences / genetics
  • Treatment Outcome

Substances

  • Acetates
  • Anti-Asthmatic Agents
  • Cyclopropanes
  • Quinolines
  • Sulfides
  • Immunoglobulin E
  • Arachidonate 5-Lipoxygenase
  • montelukast