Mandaviya Pooja R, Aïssi Dylan, Dekkers Koen F, Joehanes Roby, Kasela Silva, Truong Vinh, Stolk Lisette, Heemst Diana van, Ikram M Arfan, Lindemans Jan, Slagboom P Eline, Trégouët David-Alexandre, Uitterlinden André G, Wei Chen, Wells Phil, Gagnon France, van Greevenbroek Marleen Mj, Heijmans Bastiaan T, Milani Lili, Morange Pierre-Emmanuel, van Meurs Joyce Bj, Heil Sandra G
Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Epigenomics. 2017 Nov;9(11):1403-1422. doi: 10.2217/epi-2017-0038. Epub 2017 Oct 9.
Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes.
Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis.
Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6.
We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.
同型半胱氨酸（Hcy）是一碳代谢的敏感标志物。较高的Hcy水平与全基因组DNA低甲基化有关。我们研究了血浆Hcy与白细胞表观基因组范围的DNA甲基化之间的关联。
使用Illumina 450k芯片对来自六个队列的2035名个体进行甲基化测量。通过荟萃分析确定与Hcy相关的差异甲基化位点和区域。
分别位于19号、14号和10号染色体上的三个差异甲基化位点cg21607669（SLC27A1）、cg26382848（AJUBA）和cg10701000（KCNMA1）与Hcy显著相关。此外，我们确定了68个与Hcy相关的差异甲基化区域，其中最显著的是6号染色体上一个1.8kb的跨域区域（TNXB/ATF6B）。
我们确定了与Hcy水平相关的新的表观遗传位点，其具体作用有待进一步验证。
