Association of the cysteinyl leukotriene receptor 1 gene with atopy in the British 1958 birth cohort.
BACKGROUND
Cysteinyl leukotrienes (CysLTs) play an important role in the pathophysiology of many allergic inflammatory disorders. However, data on the contribution of genetic variability of the cysteinyl leukotriene receptor 1 gene (CYSLTR1) in asthma and atopy remain conflicting.


OBJECTIVE
We investigated the association of polymorphisms of interest located at this locus and allergic disease prevalence in a national population with an established DNA archive, the British 1958 birth cohort.


METHODS
The British 1958 birth cohort comprises all persons born in Britain during 1 week in 1958. Asthma, wheezy bronchitis, and wheezing were ascertained by interview at ages 7, 11, 16, 23, 33, and 42 years. At age 44 to 45 years, serum total circulating IgE levels were measured and atopy was defined as a serum total IgE level of greater than 30 kU/L and specific IgE levels to 1 or more of dust mite, cat fur, and mixed grass of greater than 0.3 kU/L. DNA samples from 8018 participants were genotyped for 2 variants of the CYSLTR1 promoter (Xq13-Xq21).


RESULTS
The rare polymorphism C > T (rs7066737) was not associated with any of the phenotypes studied. The common promoter polymorphism A > G (rs2806489) was not associated with total IgE levels or the prevalence or age of onset of asthma, wheezy bronchitis, or wheeze. However, the wild-type allele A was significantly associated with atopy in female subjects (chi(2) = 8.30, P = .004), although not in male subjects (P = .841).


CONCLUSIONS
These data suggest that a CYSLTR1 polymorphism previously shown to affect the gene transcription in vitro might influence the risk of atopy in the female white population with suggestive evidence of heterozygote vigor.
Duroudier
Nathalie P
NP
Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, United Kingdom. nathalie.duroudier@hotmail.fr
Strachan
David P
DP
Blakey
John D
JD
Hall
Ian P
IP
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000485:Allergens / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D018077:Receptors, Leukotriene / Q000235:genetics* / Q000276:immunology; D012737:Sex Factors; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
D000485:Allergens; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor