A polymorphism in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E

Mauro Baldini, I. Carla Lohman, Marilyn Halonen, Robert P. Erickson, Patrick G. Holt, Fernando D. Martinez

Research output: Contribution to journalArticle

743 Scopus citations

Abstract

Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-helper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens may favor the development of Th1 cells from naive CD4-positive T cells through a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble form (sCD14). The CD14 gene maps to chromosome 5q31.1, a candidate region for loci regulating total serum IgE. We hypothesized that genetic variants in the CD14 gene could influence Th-cell differentiation and thus total serum IgE. We identified a C-to-T transition at base pair - 159 from the major transcription start site (CD14/-159). Among 481 children recruited from a general population sample, frequency of allele C was 51.4%. TT homozygotes had significantly higher sCD14 levels than did carriers of both the CC and CT genotypes (P = 0.01). TT homozygotes also had significantly lower levels of IgE than did carriers of the other two genotypes, but differences were significant only among children who were skin test-positive to local aeroallergens (P = 0.004). There was no association between CD14/-159 and either interleukin (IL)-4 or interferon (IFN)-γ responses by peripheral blood mononuclear cells. However, IFN-γ and IL-4 responses were positively and negatively correlated, respectively, with serum sCD14 levels. We conclude that CD14/-159 plays a significant role in regulating serum sCD14 levels and total serum IgE levels.

Original languageEnglish (US)
Pages (from-to)976-983
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume20
Issue number5
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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