PURPOSE: CD 14 is a glycosylphosphatidylinositol linked cell surface molecule acting as a pattern recognition receptor for several bacterial motifs including lipopolysaccharide (LPS) from gram-negative bacteria and lipoarabinomannans from mycobacteria. A polymorphism on CD 14 gene promoter was associated with increased sCD14 levels in several diseases and affects the disease susceptibility and clinical outcomes. We evaluate the association between CD 14 promoter gene polymorphism (C to T transition at base pair -159) and the presence of tuberculosis in Korean population.
METHODS: The promoter gene polymorphism of CD 14 was determined by polymerase chain reaction- restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. The PGL3 plasmid constructs including -159 T or -159 C promoter of CD 14 and luciferase were transfected into human chronic myelogenous leukemia cells (K562)and human bronchial epithelial cells (BEAS-2B), and luciferase activities were estimated and compared. The levels of serum sCD 14 were measured with commercial enzyme-linked immunosorbent assay kit in tuberculosis patients and controls.
RESULTS: The frequency of the T allele was 64% in TB patients and it was more common compared with healthy controls. (57%, P=0.01) The TT genotypes were significantly overrepresented among TB patients compared with controls. (43% vs 32%, P=0.016) For the tuberculosis, the odds ratio for the TT genotype vs CC genotype was 1.60 (95% confidence interval 1.01-2.54). The TT genotypes were associated with higher promoter activities of the CD 14. Levels of serum sCD14 of 39 TB patients were higher than that of 42 healthy controls. (1851±907ug/ml vs 1191±271 ug/ml, p < 0.001).
CONCLUSION: The -159 TT genotypes in the promoter of CD 14 gene with higher promoter activity were associated with the development of TB in Koreans.
CLINICAL IMPLICATIONS: Our data suggests that sCD14, like the role in gram-negative infection, has a modulatory effects on mycobacteria-host cell interaction. Further research focused on the functional role of CD 14 in TB might contribute to elucidate the host susceptibility to development of TB.
DISCLOSURE: Young Ae Kang, No Financial Disclosure Information; No Product/Research Disclosure Information