Maruthai Kathirvel, Subramanian Mahadevan
Department of Paediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Int J Mycobacteriol. 2018 Jul-Sep;7(3):242-246. doi: 10.4103/ijmy.ijmy_86_18.
Investigation of DNA methylation in Alu repetitive elements (REs) was shown to be a promising field to explore transcriptional changes in human genome under disease condition. To scrutinize the association between Alu methylation and tuberculosis (TB) disease in children, the difference in Alu DNA methylation level was compared with healthy controls.
Whole-blood genomic DNA from 36 TB-infected children and 32 healthy controls was isolated, and the level of Alu repeat DNA methylation was examined by methylation-specific polymerase chain reaction.
The median Alu methylation level in TB patients was 30% (Interquartile range [IQR], 25-30%), whereas in healthy controls, it was 75% (IQR, 50-75%) (P < 0.0001). The median level of DNA methylation of Alu RE in TB cases was significantly lower than healthy controls. Receiver operating characteristic curve analysis showed that the area under the curve for diagnosis was 0.969 (95% confidence interval, 0.936-1) (P < 0.0001), with 100% sensitivity and 84% specificity.
Our results point out that detection of Alu DNA methylation in whole-blood DNA may be clinically useful tool for the diagnosis and prognosis of TB disease in children.
对Alu重复元件(REs)中的DNA甲基化进行研究显示,这是一个在疾病状态下探索人类基因组转录变化的有前景的领域。为了仔细研究儿童Alu甲基化与结核病(TB)之间的关联,将Alu DNA甲基化水平的差异与健康对照进行了比较。
分离了36名结核病感染儿童和32名健康对照的全血基因组DNA,并通过甲基化特异性聚合酶链反应检测Alu重复DNA甲基化水平。
结核病患者中Alu甲基化水平的中位数为30%(四分位间距[IQR],25 - 30%),而在健康对照中为75%(IQR,50 - 75%)(P < 0.0001)。结核病病例中Alu RE的DNA甲基化中位数水平显著低于健康对照。受试者工作特征曲线分析显示,诊断的曲线下面积为0.969(95%置信区间,0.936 - 1)(P < 0.0001),敏感性为100%,特异性为84%。
我们的结果指出,检测全血DNA中的Alu DNA甲基化可能是儿童结核病诊断和预后的临床有用工具。