Immunological Consequences of a Common Single Nucleotide Polymorphism

Tricia D. Levan
University of Arizona Health Sciences Center
K01ES000386

Background: A cellular receptor known as CD14 is a pattern recognition receptor that discriminates lipid-like molecules on the surface of infectious agents. Recognition of foreign agents by the receptor leads to the activation of innate host immunological defense mechanisms such as the release of inflammatory cytokines. Regulation of CD14 gene expression appears to be important in several disease states such as atopic dermatitis, HIV infection, and malaria. These investigators recently discovered a single nucleotide polymorphism (SNP) of the CD14 promoter region-a change from cytidine to thymidine at nucleotide 159.

Advance: These studies report that a common SNP in the CD14 promoter results in increased production of CD14. This SNP, known as the T polymorphism is common in Hispanic and non-Hispanic white populations. Homozygous carriers of the T allele have significant increases in serum levels of soluble CD14 along with a decrease in immunoglobulin E (IgE).

Implication: This finding suggests that CD14 may play a role in IgE synthesis and IgE mediated diseases such as allergies or asthma. The T polymorphism has also been associated with an increased risk or myocardial infarction. These findings demonstrate the broad effects that genetic variation in CD14 may have on the development of a variety of diseases.

Citation: LeVan TD, Bloom JW, Bailey TJ, Karp CL, Halonen M, Martinez FD, Vercelli D. A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity. J Immunol. 2001 Nov 15;167(10):5838-44.