期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 124, 期 3, 页码 566-U250出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2009.06.004
关键词
Atopy; asthma; British 1958 birth cohort; cysteinyl leukotriene receptor 1; genetics; leukotriene receptor
资金
- Asthma UK [05/055]
- Medical Research Council [G0000934]
- Asthma UK [05/055] Funding Source: researchfish
- Medical Research Council [G0000934] Funding Source: researchfish
- MRC [G0000934] Funding Source: UKRI
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. (J Allergy Clin Immunol 2009;124:566-72.)
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