Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE

R.W. Bottema, D.S. Postma, N.E. Reijmerink, C. Thijs, F.F. Stelma, H.A. Smit, C.P. van Schayck, B. Brunekreef, G.H. Koppelman, M. Kerkhof

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Abstract

It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Co-stimulatory molecules are crucial for the cross-talk between antigen presenting cells and T-lymphocytes which drives the IgE response. We evaluated gene-gene interactions of haplotype tagging polymorphisms in a pathway of 24 co-stimulatory genes in relation to serum IgE levels. We assessed this at ages 1-2 yrs and 6-8 yrs in 3,062 Dutch children from a pooled data set of three birth cohorts: PIAMA (Prevention and Incidence Asthma and Mite Allergy), PREVASC (Prevention of Asthma in Children) and KOALA (Child, parents and health: lifestyle and genetic constitution). Single- and multi-locus associations with serum IgE levels (3rd versus 1st tertile) were evaluated by Chi-squared tests and the multifactor dimensionality reduction (MDR) method in the following co-stimulatory genes: VTCN1, TNFRSF4, TNFRSF18, TNFRSF14, TNFSF18, TNFSF4, CD28, CTLA4, ICOS, PDCD1, BTLA, CD80, CD86, HLA-G, CD274, PDCD1LG2, CD276, LILRA4, LILRB1, LILRB2, LILRB4, CD40, ICOSLG, and CD40LG. We found multiple statistically significant single-locus ((S)) and multi-locus ((M)) associations for the genes VTCN1(SM), TNFSF18(SM), TNFSF4(S), CD28(S), CTLA4(M), ICOS(S), BTLA(M), CD80(M), CD86(SM), CD274(SM), PDCD1LG2(M), LILRA4(SM), LILRB4(M), and CD40(SM) with serum IgE. Two-locus interactions of CD86 with VTCN1 and CD274 with LILRA4 were confirmed by logistic regression. In conclusion, serum IgE levels are regulated by multiple gene-gene interaction effects in the co-stimulatory pathway. We suggest using research strategies that model multiple gene-gene interactions in genetic studies.
Original languageEnglish
Pages (from-to)54-63
JournalEuropean Respiratory Journal
Volume35
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010

Cite this

Bottema, R. W., Postma, D. S., Reijmerink, N. E., Thijs, C., Stelma, F. F., Smit, H. A., van Schayck, C. P., Brunekreef, B., Koppelman, G. H., & Kerkhof, M. (2010). Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE. European Respiratory Journal, 35(1), 54-63. https://doi.org/10.1183/09031936.00018909