Gene–vitamin D interactions on food sensitization: a prospective birth cohort study

Authors

  • X. Liu,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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  • G. Wang,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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  • X. Hong,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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  • D. Wang,

    1. Biostatistics Research Core of Children’s Memorial Research Center, Chicago, IL, USA
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  • H.-J. Tsai,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
    2. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
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  • S. Zhang,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
    2. Department of Epidemiology and Health Statistics, School of Medicine, Zhejiang University, Hangzhou, China
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  • L. Arguelles,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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  • R. Kumar,

    1. Division of Allergy and Immunology, Children’s Memorial Hospital,Chicago, IL
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  • H. Wang,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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  • R. Liu,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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  • Y. Zhou,

    1. Biostatistics Research Core of Children’s Memorial Research Center, Chicago, IL, USA
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  • C. Pearson,

    1. Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA
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  • K. Ortiz,

    1. Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA
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  • R. Schleimer,

    1. Division of Allergy–Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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  • P. G. Holt,

    1. Division of Cell Biology, Telethon Institute for Child Health Research, West Perth, WA, Australia
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  • J. Pongracic,

    1. Division of Allergy and Immunology, Children’s Memorial Hospital,Chicago, IL
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  • H. E. Price,

    1. Division of Kidney Diseases, Children’s Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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  • C. Langman,

    1. Division of Kidney Diseases, Children’s Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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  • X. Wang

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University
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Xin Liu, MD, PhD, Mary Ann and J. Milburn Smith Child Health Research Program, Children’s Memorial Hospital and Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Tel.: 312-573-7751
Fax: 312-573-7825
E-mail: xnliu@childrensmemorial.org

Abstract

To cite this article: Liu X, Wang G, Hong X, Wang D, Tsai H-J, Zhang S, Arguelles L, Kumar R, Wang H, Liu R, Zhou Y, Pearson C, Ortiz K, Schleimer R, Holt P, Pongracic J, Price HE, Langman C, Wang X. Gene–vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 2011; 66: 1442–1448.

Abstract

Background:  It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort.

Methods:  This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11 ng/ml, and FS as specific IgE ≥ 0.35 kUA/l to any of eight common food allergens in early childhood. We genotyped potentially functional single-nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs.

Results:  Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (pinteraction = 0.003, pFDR = 0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR = 1.79, 95%CI: 1.15–2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene–VDD interaction was evident (pinteraction = 9 × 10−6).

Conclusions:  Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene–vitamin D interaction on FS.

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