Does genetic regulation of IgE begin in utero? Evidence from TH1/TH2 gene polymorphisms and cord blood total IgE - 07/08/11
, Hui-Ju Tsai, PhD a, c, , Xin Liu, MD, PhD a, , Lester Arguelles, PhD a, Rajesh Kumar, MD b, Guoying Wang, MD, PhD a, Nataliya Kuptsova-Clarkson, MD, PhD a, Colleen Pearson, BA d, Kathryn Ortiz, BA d, Anthony Bonzagni, BA d, Stephanie Apollon, BA d, Lingling Fu, MS d, Jacqueline A. Pongracic, MD b, Robert Schleimer, PhD e, Patrick G. Holt, DSc f, Howard Bauchner, MD d, Xiaobin Wang, MD, MPH, ScD a, ⁎ 
Reprint requests: Xiaobin Wang, MD, MPH, ScD, Professor and Director, Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, 2300 Children’s Plaza, Box 157, Chicago, IL 60614-3394.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 ⍺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.
Le texte complet de cet article est disponible en PDF.Key words : Genetic association, candidate gene, cord blood IgE, gene-gene interaction
Abbreviations used : BMI, CBIgE, CMH, FDR, FOXP3, FS, HWE, IL4R, IL5RA, IL13RA1, JAK, LD, MAF, OR, SNP, STAT6, Treg
Plan
| 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). |
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| 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. |
Vol 126 - N° 5
P. 1059 - novembre 2010 Retour au numéro
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