TY - JOUR
T1 - Does genetic regulation of IgE begin in utero? Evidence from T H1/TH2 gene polymorphisms and cord blood total IgE
AU - Hong, Xiumei
AU - Tsai, Hui Ju
AU - Liu, Xin
AU - Arguelles, Lester
AU - Kumar, Rajesh
AU - Wang, Guoying
AU - Kuptsova-Clarkson, Nataliya
AU - Pearson, Colleen
AU - Ortiz, Kathryn
AU - Bonzagni, Anthony
AU - Apollon, Stephanie
AU - Fu, Lingling
AU - Pongracic, Jacqueline A.
AU - Schleimer, Robert
AU - Holt, Patrick G.
AU - Bauchner, Howard
AU - Wang, Xiaobin
N1 - Funding Information:
The parent study is supported in part by the March of Dimes PERI grants ( PI: X.W., 20-FY02-56 ), NIEHS ( PI: X.W., R21 ES011666 ), and NICHD ( PI: X.W., R01 HD041702 ). The follow-up study is supported in part by the Food Allergy Initiative and NIAID ( PI: X.W., R21AI079872 ). R.K. is supported by the NHLBI ( K23HL093023 ). X.L. has been supported by a career development award from the National Institutes of Health/Clinical and Translational Science Awards Program, Northwestern University ( KL2RR025740 ). X.L. also is supported by an NIAID grant ( R21AI087888 ).
Funding Information:
Disclosure of potential conflict of interest: R. Kumar has received research support from the National Heart, Lung, and Blood Institute . J. A. Pongracic has received research support from the National Institute of Allergy and Infectious Diseases and the Food Allergy Project . R. Schleimer has received research support from the National Institutes of Health . The rest of the authors have declared that they have no conflict of interest.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Candidate gene
KW - Cord blood IgE
KW - Gene-gene interaction
KW - Genetic association
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U2 - 10.1016/j.jaci.2010.08.029
DO - 10.1016/j.jaci.2010.08.029
M3 - Article
C2 - 21050946
AN - SCOPUS:78049484945
VL - 126
SP - 1059-1067.e1
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 5
ER -