TY - JOUR
T1 - Effect of day care attendance on sensitization and atopic wheezing differs by Toll-like receptor 2 genotype in 2 population-based birth cohort studies.
AU - Custovic, Adnan
AU - Rothers, Janet
AU - Stern, Debbie
AU - Simpson, Angela
AU - Woodcock, Ashley
AU - Wright, Anne L
AU - Nicolaou, Nicolaos C
AU - Hankinson, Jenny
AU - Halonen, Marilyn
AU - Martinez, Fernando D
N1 - AI 42268, NIAID NIH HHS, United StatesAI61811, NIAID NIH HHS, United StatesG0601361, Medical Research Council, United KingdomR01 AI042268, NIAID NIH HHS, United StatesR01 AI042268-14, NIAID NIH HHS, United States
PY - 2011/2
Y1 - 2011/2
N2 - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The effect of day care on sensitization and atopic wheezing may differ among children with different variants of the TLR2 gene.
AB - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The effect of day care on sensitization and atopic wheezing may differ among children with different variants of the TLR2 gene.
KW - allergic sensitization
KW - asthma
KW - birth cohorts
KW - Geneenvironment interactions
KW - TLR2
U2 - 10.1016/j.jaci.2010.10.050
DO - 10.1016/j.jaci.2010.10.050
M3 - Article
C2 - 21281869
SN - 1097-6825
VL - 127
SP - 390
EP - 397
JO - The Journal of allergy and clinical immunology
JF - The Journal of allergy and clinical immunology
IS - 2
ER -
