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

Background: The cysteinyl-leukotriene receptor type 1 (CysLT sub(1)) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC sub(4), LTD sub(4), LTE sub(4)) 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 CysLT sub(1) receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.