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 (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.


CONCLUSIONS
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.
Hao
L
L
Division of Human Genetics, University of Southampton School of Medicine, Southampton, UK.
Sayers
I
I
Cakebread
J A
JA
Barton
S J
SJ
Beghé
B
B
Holgate
S T
ST
Sampson
A P
AP
Holloway
J W
JW
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D004739:England; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D018077:Receptors, Leukotriene / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
D017931:DNA Primers; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D007073:Immunoglobulin E; C083169:leukotriene D4 receptor