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目的分析肿瘤坏死因子-α(TNF-α)基因启动子区甲基化状况与其血清中表达水平之间的相关关系,探讨表观遗传机制在职业性三氯乙烯药疹样皮炎(OMDT)发病中所起的作用。方法以OMDT患者(病例组)、三氯乙烯接触者(接触组)和正常人群(对照组)各8例为研究对象,收集周围血样品,分别采用甲基化特异性聚合酶链反应法、放射免疫法和液闪计数法检测TNF-α基因启动子区甲基化水平、血清TNF-α水平和整体基因组DNA甲基化百分比(mCpG%)。结果接触组和病例组人群TNF-α基因启动子区甲基化程度较对照组降低。病例组TNF-α水平高于对照组[(0.285±0.058)vs(0.125±0.024)ng/L,P<0.05],接触组TNF-α水平分别与对照组、病例组比较,差异均无统计学意义[(0.182±0.051)vs(0.285±0.058)、(0.182±0.051)vs(0.125±0.024)ng/L,P>0.05]。病例组mCpG%低于对照组[(61.7±5.2)%vs(79.2±4.6)%,P<0.05],接触组mCpG%分别与对照组、病例组比较,差异均无统计学意义[(73.1±6.3)%vs(79.2±4.6)%、(73.1±6.3)%vs(61.7±5.2)%,P>0.05]。结论 TNF-α基因启动子区低甲基化状态与OMDT患者血清TNF-α水平升高相关,表观遗传机制在OMDT中起重要作用。
Objective To analyze the relationship between the methylation status of tumor necrosis factor-α (TNF-α) gene promoter and its serum level and to explore the possible mechanism of epigenetic mechanism in the pathogenesis of occupational trichlorethylene dermatitis (OMDT) The role played. Methods Eight patients with OMDT (case group), trichlorethylene (contact group) and normal population (control group) were studied in this study. Peripheral blood samples were collected and analyzed by methylation-specific polymerase chain reaction The levels of TNF-α gene promoter methylation, serum TNF-α and overall genomic DNA methylation percentage (mCpG%) were detected by radioimmunoassay and liquid scintillation counting. Results The methylation of TNF-α gene in contact group and case group was lower than that in control group. The level of TNF-α in the case group was significantly higher than that in the control group [(0.285 ± 0.058) vs (0.125 ± 0.024) ng / L, P <0.05]. There was no statistical difference between the exposure group and the control group and the case group There was significant difference between the two groups ([0.182 ± 0.051] vs (0.285 ± 0.058), (0.182 ± 0.051) vs (0.125 ± 0.024) ng / L, P> 0.05]. The mCpG% in the case group was lower than that in the control group [(61.7 ± 5.2)% vs (79.2 ± 4.6)%, P <0.05], and there was no significant difference in the mCpG% ± 6.3% vs 79.2 ± 4.6%, 73.1 ± 6.3% vs 61.7 ± 5.2%, respectively. Conclusion The hypomethylation status of TNF-α gene promoter is associated with the elevation of serum TNF-α level in patients with OMDT. The epigenetic mechanism plays an important role in OMDT.