Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP
Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP
复制标题
DOI：
10.1093/hmg/ddz262
复制
发表时间：
2019-12-15
影响因子：
3.5
通讯作者：
Seielstad, Mark
中科院分区：
文献类型：
--
作者：
Albao, Dominic S.;Cutiongco-de la Paz, Eva Maria;Seielstad, Mark
虽然在不同人群中将差异甲基化位置（DMPs）与2型糖尿病（T2D）相关联方面已经做了很多工作，但并没有太多的注意力放在确定其可能的功能后果上。我们探讨了菲律宾T2D患者外周血中的甲基化变化，并确定了177个相关的DMPs。这些DMPs中的大多数与代谢、炎症和细胞周期相关的基因有关。其中三个DMP映射到TXNIP基因体，复制了T2D表观基因组关联研究（EWAS）的先前发现。TXNIP甲基化下降与3' UTR、H3K36me3组蛋白标记和Sp1结合处的转录增加一致，表明TXNIP 3' UTR处的虚假转录起始是T2D甲基化变化的功能结果。我们还探讨了在美国的菲律宾移民中T2D发病率增加的潜在表观遗传决定因素，并发现了三种与T2D和移民相互作用相关的DMP。其中两个DMP位于MAP2K7和PRMT1附近，这可能表明压力反应失调和炎症是菲律宾移民中T2D的一个促成因素。
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.