Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE
Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE
复制标题
DOI：
10.1183/09031936.00018909
复制
发表时间：
2010-01-01
影响因子：
24.3
通讯作者：
Kerkhof, M.
中科院分区：
文献类型：
--
作者：
Bottema, R. W. B.;Postma, D. S.;Kerkhof, M.
免疫球蛋白(Ig)E的产生可能是多个基因共同作用的结果。共刺激分子对抗原提呈细胞和T淋巴细胞之间的串扰至关重要，T淋巴细胞驱动IgE反应。我们评估了24个共刺激基因途径中单倍型标记多态与血清IgE水平的基因-基因交互作用。我们在1-2岁和6-8岁时对3,062名荷兰儿童进行了评估，数据集中包括三个出生队列：PIAMA(哮喘和尘螨过敏的预防和发病)、PREVASC(儿童哮喘预防)和考拉(儿童、父母和健康：生活方式和遗传构成)。通过卡方检验和多因素降维(MDR)方法，评估了以下共刺激基因VTCN1、TNFRSF4、FRSF18、TNFRSF14、TNFSF18、TNFSF4、CD28、LACT4、ICOS、PDCD1、TNBTLA、CD80、CD86、CD274、PDCD1LG2、CD276、LILRA4、LILRB1、LILRB2、LILRB4、CD40、ICOSLG和CD40LG。我们发现VTCN1(SM)、TNFSF18(SM)、TNFSF4(S)、CD28(S)、CTLA4(M)、ICOSS、BTLA(M)、CD80(M)、CD86(SM)、CD274(SM)、PD1LG2(M)、LILRA4(SM)、LILRB4(M)和CD40(SM)基因与血清IgE存在多个有统计学意义的单座位((S))和多座位((M)关联。经Logistic回归分析，CD86与VTCN1、CD274与LILRA4存在两个位点的交互作用。结论：在共刺激途径中，血清IgE水平受多基因交互作用的调节。我们建议在遗传学研究中使用模拟多基因-基因相互作用的研究策略。
It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Costimulatory 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), ICOSS, 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.