A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression
A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression
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DOI：
10.1016/j.jaci.2007.07.034
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发表时间：
2007-12-01
影响因子：
14.2
通讯作者：
Martinez, Fernando D.
中科院分区：
文献类型：
--
作者：
Bieli, Christian;Eder, Waltraud;Martinez, Fernando D.
背景资料：在生命的早期食用农场牛奶与哮喘和过敏症的减少有关。目的：我们假设先天免疫受体CD14的遗传变异可能会改变农场牛奶消费与哮喘和特应性之间的关联。方法：问卷调查数据，血清IgE水平，在来自2个欧洲人群的农民和非农民儿童中评估了CD14中4个单核苷酸多态性的基因型（过敏和内毒素研究，n = 576;预防与农业和人类生活方式相关的儿童过敏风险因素研究，n = 1539）。在一个子样本（n = 222）的CD14基因表达测定外周血白细胞。农场牛奶和CD14基因型对哮喘，过敏，和CD14表达及其相互作用的影响进行了investigated.Results：我们发现在CD14/-1721和农场牛奶消费的遗传变异之间存在显着的相互作用。农场牛奶与哮喘之间关联的校正比值比在基因型之间变化：AA，0.18（95%CI，0.07 - 0.47）; AG，0.47（95%CI，0.26 - 0.86）;和GG，0.98（95%CI，0.46 - 2.08）。在过敏性鼻结膜炎和花粉致敏的症状中观察到类似的模式。CD14/-1721也改变了农场牛奶和CD14基因表达之间的关联（校正的几何平均值比：AA，1.61（95% CI，0.98 - 2.66）; AG，I.结论：在CD14/-1721位点携带A等位基因的儿童中，食用农家奶对过敏性疾病的保护作用强于携带G等位基因纯合子的儿童。这可能是通过牛奶诱导的上调CD14基因expression.Clinical影响：我们的研究结果支持这一假设，即牛奶消费和过敏性疾病之间的负相关介导的CD14激活的先天免疫机制。
Background: Consumption of farm milk in early life is associated with less asthma and allergies.Objective: We hypothesized that genetic variation in the innate immunity receptor CD14 might modify the association between farm milk consumption and asthma and atopy.Methods: Questionnaire data, serum IgE levels, and genotypes for 4 single nucleotide polymorphisms in CD14 were assessed in farmers' and nonfarmers' children from 2 European populations (Allergy and Endotoxin study, n = 576; Prevention of Allergy Risk factors for Sensitization in children related to Farming and Anthroposophic Lifestyle study, n = 1539). In a subsample (n = 222) CD14 gene expression was measured in peripheral blood leukocytes. The effects of farm milk and CD14 genotypes on asthma, allergies, and CD14 expression and their interactions were investigated.Results: We found a significant interaction between genetic variation in CD14/-1721 and farm milk consumption. Adjusted odds ratios for the association between farm milk and asthma varied between the genotypes: AA, 0.18 (95% CI, 0.07-0.47); AG, 0.47 (95% CI, 0.26-0.86); and GG, 0.98 (95% CI, 0.46-2.08). Similar patterns were observed for symptoms of allergic rhinoconjunctivitis and pollen sensitization. CD14/-1721 also modified the association between farm milk and CD14 gene expression (adjusted geometric means ratios: AA, 1.61 (95% CI, 0.98-2.66); AG, I. 11 (95% CI, 0.71-1.72); and GG, 0.76 (95% CI, 0.39-1.48).Conclusion: The protective effect of farm milk consumption on allergic diseases is stronger in children carrying the A allele in CD14/-1721 than in children homozygous for the G allele. This might be mediated through farm milk-induced upregulated CD14 gene expression.Clinical implications: Our results support the hypothesis that the inverse association between farm milk consumption and allergic diseases is mediated by CD14-activated innate immune mechanisms.