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菲律宾 2 型糖尿病患者外周血中的甲基化变化表明 TXNIP 存在虚假转录起始。

Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP.

机构信息

Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.

National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Diliman, Quezon City 1101, Philippines.

出版信息

Hum Mol Genet. 2019 Dec 15;28(24):4208-4218. doi: 10.1093/hmg/ddz262.

Abstract

While much work has been done in associating differentially methylated positions (DMPs) to type 2 diabetes (T2D) across different populations, not much attention has been placed on identifying its possible functional consequences. We explored methylation changes in the peripheral blood of Filipinos with T2D and identified 177 associated DMPs. Most of these DMPs were associated with genes involved in metabolism, inflammation and the cell cycle. Three of these DMPs map to the TXNIP gene body, replicating previous findings from epigenome-wide association studies (EWAS) of T2D. The TXNIP downmethylation coincided with increased transcription at the 3' UTR, H3K36me3 histone markings and Sp1 binding, suggesting spurious transcription initiation at the TXNIP 3' UTR as a functional consequence of T2D methylation changes. We also explored potential epigenetic determinants to increased incidence of T2D in Filipino immigrants in the USA and found three DMPs associated with the interaction of T2D and immigration. Two of these DMPs were located near MAP2K7 and PRMT1, which may point towards dysregulated stress response and inflammation as a contributing factor to T2D among Filipino immigrants.

摘要

虽然已经有很多工作致力于在不同人群中发现与 2 型糖尿病(T2D)相关的差异甲基化位置(DMPs),但对于识别其可能的功能后果关注较少。我们探索了菲律宾 2 型糖尿病患者外周血中的甲基化变化,并鉴定出 177 个相关的 DMPs。这些 DMP 大多与代谢、炎症和细胞周期相关的基因有关。其中三个 DMP 位于 TXNIP 基因体中,复制了先前 T2D 全基因组关联研究(EWAS)的发现。TXNIP 的去甲基化与 3'UTR 的转录增加、H3K36me3 组蛋白标记和 Sp1 结合相一致,表明 TXNIP 3'UTR 的假转录起始是 T2D 甲基化变化的一个功能后果。我们还探讨了美国菲律宾移民中 T2D 发生率增加的潜在表观遗传决定因素,发现三个 DMP 与 T2D 和移民的相互作用有关。其中两个 DMP 位于 MAP2K7 和 PRMT1 附近,这可能表明应激反应和炎症失调是菲律宾移民中 T2D 的一个促成因素。

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