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同型半胱氨酸水平与白细胞DNA甲基化的细微变化相关:一项全表观基因组分析。

Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis.

作者信息

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

机构信息

Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.

Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Epigenomics. 2017 Nov;9(11):1403-1422. doi: 10.2217/epi-2017-0038. Epub 2017 Oct 9.

Abstract

AIM

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.

METHODS

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.

RESULTS

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.

CONCLUSION

We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

摘要

目的

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。

方法

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。

结果

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)。

结论

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。

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