Human Nutrition Research Centre, Newcastle University, Newcastle, UK.
Epigenetics. 2010 Jul 1;5(5):422-6. doi: 10.4161/epi.5.5.11959.
Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and no studies exist that assess its relationship with lifestyle exposures.
The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs. 5.9%; p = 0.015 and 66% vs. 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected.
AIMS & METHODS: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor-1) and N-33 (tumor suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) while gene specific methylation was quantified using the COBRA method.
For the first time, we have shown increased methylation in the promoter regions of the putative tumor suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggest that inactivation through methylation of the putative tumor suppressor genes N-33 and ESR-1 may not be associated with colorectal carcinogenesis in UC.
表观遗传标记，如 DNA 甲基化，影响基因转录和染色体稳定性，也可能受到环境暴露的影响。目前关于溃疡性结肠炎（UC）患者 DNA 甲基化谱（基因组和基因特异性甲基化）改变的研究较少，也没有研究评估其与生活方式暴露的关系。
与对照组相比，UC 患者 ESR-1 和 N-33 基因的甲基化水平均显著升高（7.9%比 5.9%；p=0.015 和 66%比 9.3%；p<0.001）。UC 患者与年龄和性别匹配的对照组之间，没有检测到全球 DNA 甲基化的差异。未发现 DNA 甲基化指数与人体测量学指标或吸烟模式之间存在相关性。
评估 UC 患者宏观正常黏膜中 ESR-1（雌激素受体-1）和 N-33（肿瘤抑制候选基因-3）基因的基因组甲基化和启动子甲基化，并研究人体测量学和生活方式暴露对 DNA 甲基化的影响。招募了 68 名受试者（24 名 UC 和 44 名年龄和性别匹配的对照组）。采集结直肠黏膜活检标本，提取 DNA。使用氚标记胞嘧啶扩展测定法（3[H] dCTP）定量基因组 DNA 甲基化，使用 COBRA 方法定量基因特异性甲基化。
我们首次在 UC 患者宏观正常黏膜中发现潜在肿瘤抑制基因 N-33 启动子区域的甲基化增加。此外，我们还证实 UC 患者的 ESR-1 启动子甲基化水平高于年龄和性别匹配的对照组。这些发现表明，在 UC 中，潜在肿瘤抑制基因 N-33 和 ESR-1 的甲基化失活可能与结直肠癌变无关。
