结核病患者全基因组甲基化与抗结核药致肝损伤关系的研究

A STUDY OF THE RELATIONSHIP BETWEEN TB PATIENTS'WHOLE-GENOME DNA METHYLATION AND ANTITUBERCULOSIS DRUG-INDUCCED LIVER INJURY

目的探讨结核病患者血浆中全基因组甲基化与抗结核药物性肝损伤(ADLI)的相关性。方法采用1∶1匹配的病例对照研究设计。接受抗结核化疗6个月内发生ADLI者160例为病例,选择与病例同居住地、年龄相差<5岁、同期未发生ADLI的结核病患者160例为对照。收集研究对象的相关信息,采集EDTA抗凝血液标本。磁珠法提取血清游离DNA,高效液相色谱法检测全基因组的甲基化水平。SPSS17.0软件用于统计学分析。结果与对照比较,既往病史、饮酒的差异均具有统计学意义(P<0.05),与ADLI的发生有关。而文化程度、婚姻、居住地、吸烟、职业的差异均无统计学意义(P>0.05)。病例和对照甲基化水平分别为(1.48±0.52)%和(8.75±1.94)%,差异有统计学意义,病例甲基化水平较低(P<0.05)。结论全基因组甲基化对ADLI的发生有明显影响,低甲基化水平的患者更易发生ADLI。

Objective To explore the correlation of whole-genome DNA methylation and antituberculosis drug-inducced liver injury in TB patients.Methods A one to one matched case control study was employed.Totally 160 cases were selected as the study cases,who accepted the anti-TB chemotherapy within six months and occurred ADLI;Based on cohabitation residence,age difference of〈5 years old,by the same anti-TB chemotherapy within six months,another 160 cases of TB patients were as controls,who did not occur ADLI.The relative factors and blood samples of each subject were collected.Serum DNA was extracted using the magnetic bead,and genome-wide methylation levels were detected by high performance liquid chromatography.SPSS17.0statistical analysis system software was employed.Results Compared with the control,history and drinking differences were statistically significant（P〈0.05）,they were the risk factors of ADLI,but education,marriage,residence,smoking,occupation were no significant difference（P〉0.05）.The whole-genome methylation level[（1.48±0.52）% vs（8.75±1.94）%]of the two groups was of statistically significant difference,the methylated of the case group was at a lower level（P〈0.05）.Conclusion The genome-wide methylation impacts the occurrence of ADLI,low methylation levels are more likely to ADLI and it is a risk factor of ADLI.