Different genetic associations of the IgE production among fetus, infancy and childhood

PLoS One. 2013 Aug 1;8(8):e70362. doi: 10.1371/journal.pone.0070362. Print 2013.

Abstract

Elevation of serum IgE levels has long been associated with allergic diseases. Many genes have been linked to IgE production, but few have been linked to the developmental aspects of genetic association with IgE production. To clarify developmental genetic association, we investigated what genes and gene-gene interactions affect IgE levels among fetus, infancy and childhood in Taiwan individuals. A birth cohort of 571 children with completion of IgE measurements from newborn to 1.5, 3, and 6 years of age was subject to genetic association analysis on the 384-customized SNPs of 159 allergy candidate genes. Fifty-three SNPs in 37 genes on innate and adaptive immunity, and stress and response were associated with IgE production. Polymorphisms of the IL13, and the HLA-DPA1 and HLA-DQA1 were, respectively, the most significantly associated with the IgE production at newborn and 6 years of age. Analyses of gene-gene interactions indentified that the combination of NPSR1, rs324981 TT with FGF1, rs2282797 CC had the highest risk (85.7%) of IgE elevation at 1.5 years of age (P=1.46 × 10(-4)). The combination of IL13, CYFIP2 and PDE2A was significantly associated with IgE elevation at 3 years of age (P=5.98 × 10(-7)), and the combination of CLEC2D, COLEC11 and CCL2 was significantly associated with IgE elevation at 6 years of age (P=6.65 × 10(-7)). Our study showed that the genetic association profiles of the IgE production among fetus, infancy and childhood are different. Genetic markers for early prediction and prevention of allergic sensitization may rely on age-based genetic association profiles.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Cohort Studies
  • Epistasis, Genetic / immunology*
  • Female
  • Fetus / immunology
  • Fetus / metabolism*
  • Humans
  • Hypersensitivity / genetics
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Infant
  • Infant, Newborn
  • Male
  • Multifactor Dimensionality Reduction
  • Polymorphism, Single Nucleotide / immunology*

Substances

  • Immunoglobulin E

Grants and funding

This work was supported by funding from the National Science Council grants: 98-3112-B-182-004 and 99-3112-B-182-004 to KDY; and Chang Gung Memorial Hospital grant: CZRPG880253. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.