CD14 C(−159)T Polymorphism Is a Risk Factor for Development of Pulmonary Tuberculosis

Abstract

Neither the expression of CD14 and Toll-like receptor 4 (TLR4) on monocytes' surface nor the mutations CD14 -159TT and TLR4 Asp299Gly have yet been evaluated as risk factors for development of pulmonary tuberculosis (TB) in the Mexican population. Level of membrane CD14 (mCD14) and membrane TLR4 (mTLR4) were determined by flow cytometry, in 104 patients with pulmonary TB (before and after treatment), 67 household contacts, and 114 healthy control subjects. Genotype/allele frequencies in CD14 -159 and TLR4 Asp299Gly were obtained by polymerase chain reaction-restriction-fragment length polymorphism. Levels of soluble CD14 (sCD14) in sera were quantified by ELISA. Higher levels of mCD14/sCD14 and mTLR4 were observed in the patients and the household contacts than in the control subjects (P<.05) and decreased in the patients after the infection was resolved. The frequency of the CD14 -159TT genotype was higher in the patients than in the control subjects (35.6% vs. 12.3%, respectively). Patients who were homozygous for allele T of the CD14 promoter gene had a significantly higher risk for development of pulmonary TB, with an odds ratio of 2.267 (95% confidence interval, 1.5%-3.3%). Levels of sCD14 or mCD14 were not associated with the CD14 -159TT genotype (P>.05). No association between TLR4 Asp299Gly and pulmonary TB was found. CD14 -159TT is a risk factor for development of pulmonary TB, whereas mCD14/sCD14 and mTLR4 are possible biomarkers for the prognosis for TB disease. CLINICAL TRIAL PROTOCOL ID: SA1168-05.