title: A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E.
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.
authors.affiliation: Respiratory Sciences Center, Department of Pediatrics and Steele Memorial Children's Research Center, and Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, USA.
authors.forename: M
authors.initials: M
authors.lastname: Baldini
authors.forename: I C
authors.initials: IC
authors.lastname: Lohman
authors.forename: M
authors.initials: M
authors.lastname: Halonen
authors.forename: R P
authors.initials: RP
authors.lastname: Erickson
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
authors.forename: F D
authors.initials: FD
authors.lastname: Martinez
mesh_terms: D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012882:Skin Tests
chemical_list: D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma