三氯乙烯对人血细胞TNF-α基因启动区甲基化影响及其表达水平研究  

Study on effect of trichloroethylene to DNA methylation of TNF-α gene promoter region in human hemocyte and its expression level

作　　者：杨建平[1] 刘益民[1] 朱志良[1] 袁建辉[2] 庄志雄[2] 

机构地区：[1]深圳市宝安区疾病预防控制中心健康检查科,广东深圳518101 [2]深圳市疾病预防控制中心,518055

出　　处：《中国职业医学》2013年第6期501-504,共4页China Occupational Medicine

基　　金：国家自然科学基金(30500599);广东省自然科学基金(9151503102000019);广东省医学科研基金(A2009606);深圳市科技计划项目(200902153);深圳市宝安科技计划项目(2008140)

摘　　要：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 correlation between the status of tumor necrosis factor-alpha （TNF-α） gene promoter methylation and its expression level in serum and to explore the effect of epigenetic mechanisms in the pathogenesis of occu- pational medicamentosa-like dermatitis of trichloroethylene （OMDT）. Methods Whole-blood samples of normal control group, triehloroethylene exposed persons （exposure group） and patients of OMDT （case group） were all collected, with 8 people in each group. The degree of TNF-α gene promoter methylation levels, serum TNF-α levels and whole DNA methyl- ation percentage （mCpG%） in each group were detected by mehtylation-specific polymerase chain reaction, radioimmuno- assay and liquid scintillation counting respectively. Results TNF-α gene promoter methylation in exposure group and case group were decreased compared with that in the control group. Serum TNF-α level in the ease group was significantly high- er than that of the control group [ （0. 285 ±0. 058） vs （0. 125 ±0. 024） ng/L,P 〈0. 05], while the level in the exposure group showed no statistical significant difference when compared with those of control group and the ease group respectively [（0.182±0.051） vs （0.285±0.058） ng/L,（0.182±0.051） vs （0.125±0.024） ng/L,P〉0.05]. Compared with that of the control group, mCpG% in the exposure group was reduced [ （61.7 ±5.2）% vs （79. 2 ±4.6）% ,P 〈0. 05], while the exposure group showed no statistical significant difference compared with the control group and the case group re- spectively [ （ 73.1 ± 6. 3 ） % vs （ 79. 2 ±4. 6 ） %, （ 73.1±6. 3 ） % vs （ 61.7 ±5.2 ） %, P 〉 0. 05 ]. Conclusion There is correlation between the TNF-α gene promoter low methylation status and the increase of serum TNF-α concentration in OM- DT patients. It suggests that epigenetic mechanism play an important role on OMDT.

关 键 词：三氯乙烯 肿瘤坏死因子-Α DNA甲基化 启动子 

分 类 号：R135.1[医药卫生—劳动卫生]