PT  - JOURNAL ARTICLE
AU  - N.E. Reijmerink
AU  - M. Kerkhof
AU  - R.W.B. Bottema
AU  - J. Gerritsen
AU  - F.F. Stelma
AU  - C. Thijs
AU  - C.P. van Schayck
AU  - H.A. Smit
AU  - B. Brunekreef
AU  - D.S. Postma
AU  - G.H. Koppelman
TI  - Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy
AID  - 10.1183/09031936.00099210
DP  - 2011 Jan 01
TA  - European Respiratory Journal
PG  - erj00992-2010
4099  - http://erj.ersjournals.com/content/early/2011/02/24/09031936.00099210.short
4100  - http://erj.ersjournals.com/content/early/2011/02/24/09031936.00099210.full
AB  - Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system.To assess whether interactions between microbial exposures and genes encoding TLRs (related) genes result in atopy.Genes, environmental factors and gene-environment interactions of 66 SNPs of 12 genes (TLR 1-6 and 9-10, CD14, MD2, LBP and Dectin-1) and six proxy parameters of microbial exposure (i.e. sibship size, pets, day-care and tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (The Allergenic study).The presence of ≥2 older siblings increased the risk to develop high total IgE levels at different ages. This risk increased further in children aged 1–2 years carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two and three factor gene-gene and gene-environment interactions were found (e.g between sibship size, day-care and LBP SNP rs2232596)Larger sibship size is associated with increased total IgE levels. Furthermore, complex 2 and 3 factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.