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

Am J Respir Cell Mol Biol. 1999 May;20(5):976-83. doi: 10.1165/ajrcmb.20.5.3494.

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)-gamma responses by peripheral blood mononuclear cells. However, IFN-gamma 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Child
  • DNA Primers
  • Genotype
  • Humans
  • Immunoglobulin E / blood*
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharide Receptors / genetics*
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Skin Tests

Substances

  • DNA Primers
  • Lipopolysaccharide Receptors
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma

Associated data

  • GENBANK/AF097335