Duroudier Nathalie P, Strachan David P, Blakey John D, Hall Ian P
Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, United Kingdom.
J Allergy Clin Immunol. 2009 Sep;124(3):566-72, 572.e1-3. doi: 10.1016/j.jaci.2009.06.004.
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.
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.
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).
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).
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.
半胱氨酰白三烯（CysLTs）在多种过敏性炎症性疾病的病理生理学中起重要作用。然而，关于半胱氨酰白三烯受体1基因（CYSLTR1）遗传变异在哮喘和特应性疾病中的作用的数据仍存在矛盾。
我们在拥有完善DNA存档的英国1958年出生队列这一全国性人群中，研究了该基因座上感兴趣的多态性与过敏性疾病患病率之间的关联。
英国1958年出生队列包括1958年某一周内在英国出生的所有人。通过在7岁、11岁、16岁、23岁、33岁和42岁时进行访谈来确定哮喘、喘息性支气管炎和喘息情况。在44至45岁时，测量血清总循环IgE水平，特应性定义为血清总IgE水平大于30 kU/L，以及对尘螨、猫毛和混合草中1种或更多种的特异性IgE水平大于0.3 kU/L。对8018名参与者的DNA样本进行CYSLTR1启动子（Xq13 - Xq21）的2种变体基因分型。
罕见的多态性C>T（rs7066737）与所研究的任何表型均无关联。常见的启动子多态性A>G（rs2806489）与总IgE水平、哮喘、喘息性支气管炎或喘息的患病率及发病年龄均无关联。然而，野生型等位基因A与女性受试者的特应性显著相关（χ² = 8.30，P = 0.004），而在男性受试者中则无关联（P = 0.841）。
这些数据表明，先前显示在体外影响基因转录的CYSLTR1多态性可能会影响女性白种人群的特应性风险，并有杂合子优势的提示性证据。
