Dataset Information

Does genetic regulation of IgE begin in utero? Evidence from T(H)1/T(H)2 gene polymorphisms and cord blood total IgE.

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 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 × 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 ?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.

SUBMITTER: Hong X

PROVIDER: S-EPMC3020083 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Publications

Does genetic regulation of IgE begin in utero? Evidence from T(H)1/T(H)2 gene polymorphisms and cord blood total IgE.

Hong Xiumei X Tsai Hui-Ju HJ Liu Xin X Arguelles Lester L Kumar Rajesh R Wang Guoying G Kuptsova-Clarkson Nataliya N Pearson Colleen C Ortiz Kathryn K Bonzagni Anthony A Apollon Stephanie S Fu Lingling L Pongracic Jacqueline A JA Schleimer Robert R Holt Patrick G PG Bauchner Howard H Wang Xiaobin X

The Journal of allergy and clinical immunology 20101101 5

<h4>Background</h4>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.<h4>Objective</h4>To test the associations between f ...[more]

PMID: 21050946

Similar Datasets

Project description:BackgroundIL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene-gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene-gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population.Methods989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene-gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods.ResultsA four-way gene-gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10-4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10-3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10-2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10-2).ConclusionsGene-gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

Dataset Information

Does genetic regulation of IgE begin in utero? Evidence from T(H)1/T(H)2 gene polymorphisms and cord blood total IgE.

Background

Objective

Methods

Results

Conclusion

Publications

Does genetic regulation of IgE begin in utero? Evidence from T(H)1/T(H)2 gene polymorphisms and cord blood total IgE.

Similar Datasets

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