ty - jour t1 - t细胞的相互作用和抗原呈递细胞共刺激基因在儿童咽部jf - 欧洲呼吸杂志jo - 欧元reshir j sp - 54 lp - 63 do - 10.1183 / 09031936.00018909 vl - 35是 - 1 au -Bottema, R. W. B. AU - Postma, D. S. AU - Reijmerink, N. E. AU - Thijs, C. AU - Stelma, F. F. AU - Smit, H. A. AU - van Schayck, C. P. AU - Brunekreef, B. AU - Koppelman, G. H. AU - Kerkhof, M. Y1 - 2010/01/01 UR - //www.qdcxjkg.com/content/35/1/54.abstract N2 - 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 VTCN1SM, TNFSF18SM, TNFSF4S, CD28S, CTLA4M, ICOSS, BTLAM, CD80M, CD86SM, CD274SM, PDCD1LG2M, LILRA4SM, LILRB4M, and CD40SM 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. ER -