Does genetic regulation of IgE begin in utero? Evidence from TH1/TH2 gene polymorphisms and cord blood total IgE

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:126

Article

Hong, Xiumei²  Tsai, Hui-Ju^2,4  Liu, Xin²  Arguelles, Lester²  Kumar, Rajesh³  Wang, Guoying²  Kuptsova-Clarkson, Nataliya²  Pearson, Colleen^5,6  Ortiz, Kathryn^5,6  Bonzagni, Anthony^5,6  Apollon, Stephanie^5,6  Fu, Lingling^5,6  Pongracic, Jacqueline A.³  Schleimer, Robert⁷  Holt, Patrick G.⁸  Bauchner, Howard⁵  Wang, Xiaobin^1,2 

[1] Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Mary Ann & J Milburn Smith Child Hlth Res Program, Chicago, IL 60614 USA

[2] Childrens Mem Hosp, Childrens Mem Res Ctr, Chicago, IL 60614 USA

[3] Childrens Mem Hosp, Div Allergy & Immunol, Chicago, IL 60614 USA

[4] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan

[5] Boston Univ, Sch Med, Dept Pediat, Chicago, IL USA

[6] Boston Med Ctr, Chicago, IL USA

[7] Northwestern Univ, Div Allergy Immunol, Feinberg Sch Med, Chicago, IL 60614 USA

[8] Telethon Inst Child Hlth Res, Div Cell Biol, Perth, WA, Australia

关键词: Genetic association;    candidate gene;    cord blood IgE;    gene-gene interaction;   

DOI  :  10.1016/j.jaci.2010.08.029

来源: Elsevier

【 摘 要 】

Background: Elucidation of early life factors is critical to understand the development of allergic diseases, especially those manifesting in early life such as food allergies and atopic dermatitis. Cord blood IgE (CBIgE) is a recognized risk factor for the subsequent development of allergic diseases. In contrast with numerous genetic studies of total serum IgE in children and adults, limited genetic studies on CBIgE have been conducted. Objective: To test the associations between functional or tagging single nucleotide polymorphisms (SNPs) in genes involved in the T(H)1/T(H)2 pathway and CBIgE in a large US inner-city birth cohort. Methods: CBIgE, measured by Phadia ImmnunoCAP, was analyzed as a continuous and a binary variable. The association of each SNP with the 2 outcomes was tested using tobit and logistic regression models, respectively, with adjustment for pertinent covariates, ancestral proportion, and multiple testing. Ethnic heterogeneity and gene-gene interactions were also explored. Results: Three SNPs (rs1800925, rs2069743, and rs1295686) in the IL13 gene were significantly associated with CBIgE concentration (P <= 6 x 10(-4), FDR-corrected P < .05). These SNPs jointly influenced CBIgE in a dose-response manner (P for trend = 9 x 10(-8)). Significant associations also were observed for SNPs in the IL-13 receptor alpha 1 (rs5956080) and signal transducer and activator of transcription 6 (rs11172106) genes. Ethnicity-specific genetic effects were observed for SNPs in the IL5 and GATA3 genes. Several gene-gene interactions (including IL13-IL4 receptor and IL13-signal transducer and activator of transcription 6 interactions) were detected in relation to CBIgE. Conclusion: Our data demonstrated that multiple SNPs were individually and jointly associated with CBIgE, with evidence of gene-gene interactions and ethnic heterogeneity. These findings suggest that genetic regulation of IgE may begin in utero. (J Allergy Clin Immunol 2010;126:1059-67.)

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