Does genetic regulation of IgE begin in utero? Evidence from T H1/TH2 gene polymorphisms and cord blood total IgE

Xiumei Hong, Hui Ju Tsai, Xin Liu, Lester Arguelles, Rajesh Kumar, Guoying Wang, Nataliya Kuptsova-Clarkson, Colleen Pearson, Kathryn Ortiz, Anthony Bonzagni, Stephanie Apollon, Lingling Fu, Jacqueline A. Pongracic, Robert Schleimer, Patrick G. Holt, Howard Bauchner, Xiaobin Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 TH1/TH2 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 × 10-4, FDR-corrected P < .05). These SNPs jointly influenced CBIgE in a dose-response manner (P for trend = 9 × 10-8). Significant associations also were observed for SNPs in the IL-13 receptor α1 (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.

Original languageEnglish (US)
Pages (from-to)1059-1067.e1
JournalJournal of Allergy and Clinical Immunology
Volume126
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • Candidate gene
  • Cord blood IgE
  • Gene-gene interaction
  • Genetic association

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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