Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht and Care and Public Health Research Institute, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
J Allergy Clin Immunol. 2010 Jan;125(1):231-6.e1-5. doi: 10.1016/j.jaci.2009.10.011.
Perturbations in the gut microbiota have been linked to atopic diseases. However, the development of atopic diseases depends not only on environmental factors (like microbial stimulation) but also on genetic factors. It is likely that particularly gene-environmental interactions in early life determine the development of atopy.
We examine the interaction between detection of fecal Escherichia coli and genetic variations in the CD14 and Toll-like receptor 4 (TLR4) genes in relation to atopic manifestations.
Within the Child, Parent and Health: Lifestyle and Genetic Constitution (KOALA) Birth Cohort Study, fecal samples of 957 one-month-old infants were collected and quantitatively screened for E coli. Fourteen haplotype-tagging polymorphisms in the genes TLR4 and CD14 were genotyped in 681 of the 957 children. Atopic outcomes were parentally reported eczema in the first 2 years of life and clinically diagnosed eczema and allergic sensitization at age 2 years. Multiple logistic regression was used to evaluate a multiplicative model of interaction.
Most of the single nucleotide polymorphisms (SNPs) showed no significant interaction with E coli exposure for both eczema and allergic sensitization. A borderline significant multiplicative interaction was found between E coli and the rs2569190 (CD14/-159) SNP regarding allergic sensitization. Furthermore, a statistically significant multiplicative interaction was found for the TLR4 SNP rs10759932 (P for interaction = .001). E coli colonization was associated with a decreased risk of sensitization only in children with the rs10759932 TT genotype (adjusted odds ratio, 0.31; 95% CI, 0.14-0.68) and not in children with the minor C allele. This interaction remained statistically significant after controlling for multiple testing.
The current study is the first to address the potential effect-modifying role of genetic variations in the relationship between the intestinal microbiota and allergy development.
肠道微生物群的紊乱与特应性疾病有关。然而，特应性疾病的发展不仅取决于环境因素（如微生物刺激），还取决于遗传因素。很可能是生命早期特定的基因-环境相互作用决定了特应性的发展。
我们研究粪便大肠杆菌的检出与 CD14 和 Toll 样受体 4（TLR4）基因遗传变异之间的相互作用与特应性表现的关系。
在儿童、父母和健康：生活方式和遗传构成（KOALA）出生队列研究中，收集了 957 名一个月大婴儿的粪便样本，并对粪便样本进行定量筛选以检测大肠杆菌。在 957 名儿童中的 681 名儿童中，对 TLR4 和 CD14 基因的 14 个单倍型标记多态性进行了基因分型。特应性结局是父母在生命的头 2 年报告的湿疹和 2 岁时临床诊断的湿疹和过敏致敏。采用多因素逻辑回归评估交互作用的乘法模型。
大多数单核苷酸多态性（SNP）与大肠杆菌暴露对湿疹和过敏致敏均无显著交互作用。大肠杆菌与 CD14/-159(rs2569190)SNP 之间存在边缘显著的乘法交互作用，与过敏致敏有关。此外，TLR4 基因 rs10759932(SNP)的统计学显著乘法交互作用（交互作用的 P 值为.001）。只有在携带 rs10759932 TT 基因型的儿童中，大肠杆菌定植与致敏风险降低相关（调整后的比值比，0.31；95%CI，0.14-0.68），而不是在携带次要 C 等位基因的儿童中。在进行多重检验控制后，这种相互作用仍然具有统计学意义。
本研究首次探讨了遗传变异在肠道微生物群与过敏发展之间的潜在效应修饰作用。
