The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma

Clin Exp Allergy. 2006 Jun;36(6):735-41. doi: 10.1111/j.1365-2222.2006.02511.x.

Abstract

Background: The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma.

Methods: Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined.

Results: Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s.

Conclusion: Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asthma / immunology
  • Child
  • Child, Preschool
  • DNA Primers / genetics
  • England
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hypersensitivity / ethnology
  • Hypersensitivity / genetics*
  • Hypersensitivity / immunology
  • Immunoglobulin E / blood
  • Male
  • Membrane Proteins / genetics*
  • Polymorphism, Genetic*
  • Receptors, Leukotriene / genetics*
  • Sequence Analysis, DNA / methods

Substances

  • DNA Primers
  • Membrane Proteins
  • Receptors, Leukotriene
  • Immunoglobulin E
  • leukotriene D4 receptor