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维生素D受体基因多态性与肺结核患者痰菌转阴时间

Vitamin D receptor gene polymorphisms and sputum conversion time in pulmonary tuberculosis patients.

作者信息

Babb C, van der Merwe L, Beyers N, Pheiffer C, Walzl G, Duncan K, van Helden P, Hoal E G

机构信息

Molecular Biology and Human Genetics, DST/NRF Centre of Excellence in Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Stellenbosch University, Tygerberg, South Africa.

出版信息

Tuberculosis (Edinb). 2007 Jul;87(4):295-302. doi: 10.1016/j.tube.2007.03.001. Epub 2007 Apr 20.

Abstract

A cohort of pulmonary tuberculosis (TB) patients in a South African admixed population was investigated to determine if the vitamin D receptor gene (VDR) polymorphisms FokI, ApaI, and TaqI are associated with TB susceptibility or time to sputum conversion, and to investigate other clinical and demographic factors affecting the rate of response to treatment. Firstly, a case-control association study of 249 TB cases and 352 healthy controls was carried out to investigate association of VDR polymorphisms with TB susceptibility. Secondly, a cohort of pulmonary tuberculosis patients with conversion times for both sputum smear (n=220) and culture (n=222) were analysed to determine factors contributing to mycobacterial resolution in sputum. Age and gender adjusted Cox regression models were constructed. Our results indicate that the extent of disease at diagnosis was predictive of both smear and culture conversion times in the final models. Smoking status and VDR genotype contributed independently to smear conversion time, with ApaI 'AA' genotype and TaqI 'T'-containing genotypes predictive of a faster response to TB chemotherapy. We did not find an association between VDR genotype and TB in the case-control study. We conclude that the time taken for an individual to convert to sputum negativity while on antituberculosis therapy can be independently predicted by the VDR genotype.

摘要

在南非混合人群中对一组肺结核(TB)患者进行了调查,以确定维生素D受体基因(VDR)多态性FokI、ApaI和TaqI是否与结核病易感性或痰菌转阴时间相关,并研究影响治疗反应率的其他临床和人口统计学因素。首先,对249例结核病病例和352例健康对照进行了病例对照关联研究,以调查VDR多态性与结核病易感性的关联。其次,对一组痰涂片(n = 220)和培养(n = 222)转阴时间的肺结核患者进行分析,以确定有助于痰液中分枝杆菌清除的因素。构建了年龄和性别调整的Cox回归模型。我们的结果表明,在最终模型中,诊断时的疾病程度可预测涂片和培养转阴时间。吸烟状况和VDR基因型独立影响涂片转阴时间,ApaI 'AA'基因型和含TaqI 'T'的基因型预示对结核病化疗反应更快。在病例对照研究中,我们未发现VDR基因型与结核病之间存在关联。我们得出结论,个体在接受抗结核治疗期间痰菌转阴所需的时间可由VDR基因型独立预测。

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