Kang Young Ae, Lee Hye Won, Kim Young Whan, Han Sung Koo, Shim Young-Soo, Yim Jae-Joon
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
FEMS Immunol Med Microbiol. 2009 Dec;57(3):229-35. doi: 10.1111/j.1574-695X.2009.00602.x. Epub 2009 Aug 21.
The aim of the present study was to confirm the association between the CD14-159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14-159C/T genotypes were determined by PCR - restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter-luciferase reporter constructs, including the -159T or -159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-gamma secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of -159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the -159T allele was higher than that of the -159C allele. Serum sCD14 levels were higher among tuberculosis patients with -159TT genotypes than among those with -159CC genotypes and interferon-gamma release by PBMCs was decreased in subjects with -159TT genotypes. In conclusion, the -159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the -159T allele, the higher level of sCD14, and the decreased interferon-gamma secretion in subjects with -159TT genotypes.
本研究的目的是证实韩国人群中CD14 - 159C/T多态性与结核病之间的关联，并阐明这种假定关联的功能基础。通过聚合酶链反应 - 限制性片段长度多态性分析，在274例结核病患者和422例健康对照中确定了CD14 - 159C/T基因型。将包含 - 159T或 - 159C等位基因的重组CD14启动子 - 荧光素酶报告基因构建体转染到K562和BEAS - 2B细胞中，并测量和比较荧光素酶活性。使用酶联免疫吸附测定法测量外周血单核细胞（PBMC）分泌的血清可溶性CD14（sCD14）和干扰素 - γ水平。结核病患者中 - 159TT基因型的频率高于健康对照。 - 159T等位基因的启动子活性高于 - 159C等位基因。 - 159TT基因型的结核病患者血清sCD14水平高于 - 159CC基因型的患者，并且 - 159TT基因型的受试者中PBMC释放的干扰素 - γ减少。总之， - 159TT CD14基因型与韩国人结核病的发生有关。这种关联可能是由于 - 159T等位基因较高的启动子活性、较高的sCD14水平以及 - 159TT基因型受试者中干扰素 - γ分泌减少所致。
