Roth Daniel E, Soto Giselle, Arenas Fanny, Bautista Christian T, Ortiz Jaime, Rodriguez Richard, Cabrera Lilia, Gilman Robert H
Asociación Benéfica Proyectos en Informática, Salud, Medicina y Agricultura, Cayetano Heredia University, Lima, Peru.
J Infect Dis. 2004 Sep 1;190(5):920-7. doi: 10.1086/423212. Epub 2004 Jul 29.
Polymorphisms in the gene that encodes the vitamin D receptor (VDR) may influence the host response to Mycobacterium tuberculosis infection.
In a Peruvian community with a high incidence of tuberculosis (TB), VDR TaqI and FokI polymorphisms were compared among 103 patients with pulmonary TB and 206 matched healthy control subjects. Associations of VDR polymorphisms with treatment outcome were analyzed among 78 patients undergoing treatment of pulmonary TB.
Sputum mycobacterial culture and auramine stain conversions were significantly faster among participants with the FokI FF genotype, compared with participants with the non-FF genotypes. Sputum culture conversion was faster among participants with the TaqI Tt genotype, compared with those with the TT genotype. Increased probability of culture conversion during TB treatment was independently associated with the TaqI Tt genotype (age- and sex-adjusted relative risk, 4.28; 95% confidence interval, 1.88-9.75; P = .001). VDR polymorphisms were not significantly associated with susceptibility to TB in the case-control study.
VDR gene polymorphisms are associated with the time to sputum culture and auramine stain conversion during TB treatment. To our knowledge, the present study is the first report of a specific host gene influence on the outcome of TB treatment. These findings demonstrate the potential clinical relevance of immunomodulatory functions of vitamin D metabolites acting via the VDR in the host response against pulmonary TB.
编码维生素D受体(VDR)的基因多态性可能影响宿主对结核分枝杆菌感染的反应。
在结核病(TB)高发的秘鲁社区,对103例肺结核患者和206例匹配的健康对照者进行VDR TaqI和FokI基因多态性比较。对78例接受肺结核治疗的患者分析VDR基因多态性与治疗结果的相关性。
与非FokI FF基因型参与者相比,FokI FF基因型参与者的痰分枝杆菌培养和金胺染色转阴明显更快。与TT基因型参与者相比,TaqI Tt基因型参与者的痰培养转阴更快。结核病治疗期间培养转阴概率增加与TaqI Tt基因型独立相关(年龄和性别调整后的相对风险为4.28;95%置信区间为1.88 - 9.75;P = 0.001)。在病例对照研究中,VDR基因多态性与结核病易感性无显著相关性。
VDR基因多态性与结核病治疗期间痰培养和金胺染色转阴时间相关。据我们所知,本研究是关于特定宿主基因对结核病治疗结果影响的首次报道。这些发现证明了维生素D代谢产物通过VDR在宿主抗肺结核反应中的免疫调节功能的潜在临床相关性。