Genomic Research on Complex Diseases (GRC Group), CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, 500 007, India.
Building No 7, School of Basic & Applied Sciences, Dayananda Sagar University, Shavige Malleshwara Hills, Kumaraswamy Layout, Bangalore 560 078, Karnataka, India.
Epigenomics. 2018 Jan;10(1):71-90. doi: 10.2217/epi-2017-0102. Epub 2017 Nov 14.
To investigate the effect of B and/or folic acid supplementation on genome-wide DNA methylation.
We performed Infinium HumanMethylation450 BeadChip (Zymo Research, CA, USA) assay in children supplemented with B and/or folic acid (n = 12 in each group) and investigated the functional mechanism of selected differentially methylated loci.
We noted significant methylation changes postsupplementation in B (589 differentially methylated CpGs and 2892 regions) and B + folic acid (169 differentially methylated CpGs and 3241 regions) groups. Type 2 diabetes-associated genes TCF7L2 and FTO; and a miRNA, miR21 were further investigated in another B-supplementation cohort. We also demonstrate that methylation influences miR21 expression and FTO, TCF7L2, CREBBP/CBP and SIRT1 are direct targets of miR21-3p.
B supplementation influences regulation of several metabolically important Type 2 diabetes-associated genes through methylation of miR21. Hence, our study provides novel epigenetic explanation for the association between disordered one carbon metabolism and risk of adiposity, insulin resistance and diabetes and has translational potential.
研究 B 族维生素和/或叶酸补充对全基因组 DNA 甲基化的影响。
我们对补充 B 族维生素和/或叶酸的儿童（每组 12 人）进行了 Infinium HumanMethylation450 BeadChip（Zymo Research，CA，USA）检测，并研究了选定的差异甲基化位点的功能机制。
我们注意到补充 B 族维生素后（589 个差异甲基化 CpG 和 2892 个区域）和 B 族维生素+叶酸后（169 个差异甲基化 CpG 和 3241 个区域）有显著的甲基化变化。我们还在另一项 B 族维生素补充队列中进一步研究了 2 型糖尿病相关基因 TCF7L2 和 FTO；以及一种 miRNA，miR21。我们还证明，甲基化影响 miR21 的表达，FTO、TCF7L2、CREBBP/CBP 和 SIRT1 是 miR21-3p 的直接靶基因。
B 族维生素补充通过 miR21 的甲基化影响几种与代谢有关的 2 型糖尿病相关基因的调控。因此，我们的研究为紊乱的一碳代谢与肥胖、胰岛素抵抗和糖尿病风险之间的关联提供了新的表观遗传学解释，并具有转化潜力。
