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维生素 D 和钙敏感受体基因启动子中 CpG 岛的甲基化状态并不能解释甲状旁腺腺瘤中基因表达的降低。

Methylation status of the CpG islands in vitamin D and calcium-sensing receptor gene promoters does not explain the reduced gene expressions in parathyroid adenomas.

机构信息

AssociateDepartment of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012.

出版信息

J Clin Endocrinol Metab. 2013 Oct;98(10):E1631-5. doi: 10.1210/jc.2013-1699. Epub 2013 Aug 2.

Abstract

AIM

The exact mechanism causing decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CASR) genes in parathyroid adenoma is not known, but methylation of promoter regions is often detected during epigenetic downregulation of gene expression. We investigated whether epigenetic silencing is involved in the decreased expression of VDR and CASR.

EXPERIMENTAL DESIGN

Real-time PCR and immunohistochemistry confirmed the downregulation of the VDR and CASR genes at transcriptional and translational levels. Bisulfite-converted DNA samples from parathyroid adenomas with control samples were analyzed for methylation in the promoter region of VDR and CASR genes.

RESULTS

There was no significant methylation in the promoter regions of VDR and CASR genes in parathyroid adenomatous tissues.

CONCLUSIONS

Methylation-mediated silencing of VDR and CASR promoter does not appear to be associated with reduced expression, indicating the involvement of other factors in specific suppression of VDR and CASR in parathyroid adenomas.

摘要

目的

甲状旁腺腺瘤中维生素 D 受体(VDR)和钙敏感受体(CASR)基因表达下调的确切机制尚不清楚,但在基因表达的表观遗传下调过程中,经常会检测到启动子区域的甲基化。我们研究了表观遗传沉默是否参与了 VDR 和 CASR 的表达下调。

实验设计

实时 PCR 和免疫组织化学证实 VDR 和 CASR 基因在转录和翻译水平下调。对甲状旁腺瘤的亚硫酸氢盐转化 DNA 样本与对照样本进行分析,以检测 VDR 和 CASR 基因启动子区域的甲基化情况。

结果

甲状旁腺瘤组织中 VDR 和 CASR 基因启动子区域无明显甲基化。

结论

VDR 和 CASR 启动子的甲基化介导沉默似乎与表达下调无关,这表明在甲状旁腺瘤中 VDR 和 CASR 的特异性抑制涉及其他因素。

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