University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
J Allergy Clin Immunol. 2011 Feb;127(2):390-397.e1-9. doi: 10.1016/j.jaci.2010.10.050.
Variation in the Toll-like receptor 2 gene (TLR2/-16934) is associated with allergic diseases among farmers' children but not among children not living on farms.
To test the hypothesis that the same genetic variant conferring protection in the farming environment is associated with reduced risk of developing allergic phenotypes among urban children attending day care in early life.
In 2 population-based birth cohorts (Manchester, United Kingdom, Manchester Asthma and Allergy Study [MAAS]; Tucson, Ariz, Tucson Infant Immune Study [IIS]), participants were recruited prenatally and followed prospectively (MAAS: 3, 5, 8 and 11 years; IIS: 1, 2, 3 and 5 years). We assessed allergic sensitization and atopic wheezing at each follow-up.
A total of 727 children participated in Manchester and 263 in Tucson. We found no significant associations between TLR2/-16934 and sensitization and atopic wheeze in either cohort. However, a different pattern emerged when we explored the interaction between TLR2/-16934 and day care attendance on these outcomes. We found a significant interaction between day care and TLR2/-16934 on the development of sensitization in the longitudinal model in MAAS in that children carrying the T allele who attended day care were less likely to be sensitized than those who did not attend day care, whereas among AA homozygotes, the association tended to be in the opposite direction. In a longitudinal model in IIS, we found a significant interaction between day care attendance and TLR2/-16934 on the development atopic wheezing. Significant interactions between TLR2/-16934 and day care were maintained when adjusting for socioeconomic status.
The effect of day care on sensitization and atopic wheezing may differ among children with different variants of the TLR2 gene.
Toll 样受体 2 基因（TLR2/-16934）的变异与农民子女的过敏性疾病有关，但与不住在农场的儿童无关。
检验以下假设，即在农业环境中具有保护作用的相同遗传变异与城市儿童在早期日托中发生过敏表型的风险降低有关。
在两个基于人群的出生队列中（英国曼彻斯特的曼彻斯特哮喘和过敏研究[MAAS]；亚利桑那州图森的图森婴儿免疫研究[IIS]），参与者在产前招募并进行前瞻性随访（MAAS：3、5、8 和 11 岁；IIS：1、2、3 和 5 岁）。我们在每次随访时评估过敏致敏和特应性喘息。
共有 727 名儿童参加了曼彻斯特研究，263 名儿童参加了图森研究。我们在两个队列中均未发现 TLR2/-16934 与致敏和特应性喘息之间存在显著关联。然而，当我们探索 TLR2/-16934 与日托对这些结果的交互作用时，出现了不同的模式。我们发现 TLR2/-16934 与日托之间在 MAAS 的纵向模型中对致敏发展的交互作用具有显著性，即携带 T 等位基因且参加日托的儿童比未参加日托的儿童致敏的可能性较小，而在 AA 纯合子中，这种关联的趋势则相反。在 IIS 的纵向模型中，我们发现日托参与和 TLR2/-16934 之间对特应性喘息发展的交互作用具有显著性。在调整社会经济地位后，TLR2/-16934 与日托之间的显著相互作用仍然存在。
TLR2/-16934 基因不同变异体的儿童，日托对致敏和特应性喘息的影响可能不同。
