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

Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-he lper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens ma y favor the development of Th1 cells from naive CD4-positive T cells throug h a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble fo rm (sCD14). The CD14 gene maps to chromosome 5q131.1, a candidate region fo r 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 t ranscription start site (CD14/-159). Among 481 children recruited from a ge neral population sample, frequency of allele C was 51.4%. TT homozygotes ha d significantly higher sCD 14 levels than did carriers of both the CC and C T genotypes (P = 0.01). TT homozygotes also had significantly lower levels of IgE than did carriers of the other two genotypes, but differences were s ignificant only among children who were skin test-positive to local aeroall ergens (P = 0.004). There was no association between CD14/-159 and either i nterleukin (IL)-4 or interferon (IFN)-gamma responses by peripheral blood m ononuclear cells. However, IFN-gamma and IL-4 responses were positively and negatively correlated, respectively, with serum sCD 14 levels. We conclude that CD14/-159 plays a significant role in regulating serum sCD14 levels a nd total serum IgE levels.