Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.
Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.
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DOI：
10.1371/journal.pone.0065744
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Arola L
中科院分区：
文献类型：
--
作者：
Crescenti A;Solà R;Valls RM;Caimari A;Del Bas JM;Anguera A;Anglés N;Arola L
DNA甲基化调节基因表达，并且可以通过食物中的不同生物活性化合物（如多酚）进行修饰。可可是多酚类物质的丰富来源，但其在DNA甲基化中的作用仍不清楚。目的是评估可可消费对DNA甲基化的影响，并确定参与DNA甲基化过程的酶是否参与可可在人类中发挥这些作用的机制。在214名高血压前期、1期高血压或高胆固醇血症志愿者中评估外周血中的总体DNA甲基化水平。志愿者被分为两组：110名受试者食用可可（6克/天）两周，104名对照受试者。此外，用可可提取物处理6名受试者的外周血单核细胞（PBMC），以分析DNA甲基转移酶（DNMT）、亚甲基四氢叶酸还原酶（MTHFR）和甲硫氨酸合成酶还原酶（MTRR）基因的mRNA水平。食用可可显著降低了DNA甲基化水平（2.991±0.366对3.909±0.380，p<0.001）。此外，我们发现可可对DNA甲基化的影响与MTHFR，MTRR和DNMT 3B基因中的三种多态性之间存在关联。此外，在PBMC中，可可提取物显著降低了DNMT、MTHFR和MTRR的mRNA水平。我们的研究首次表明，可可的消费降低了具有心血管危险因素的人外周血白细胞的整体DNA甲基化。PBMC的体外实验表明，可可可能部分通过下调DNMT、MTHFR和MTRR发挥这种作用，这些基因是参与这一表观遗传过程的关键基因。 Clinicaltrials.gov NCT 00511420和NCT 00502047
DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process. Clinicaltrials.gov NCT00511420 and NCT00502047
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影响因子：
5.8
作者：
Link, Alexander;Balaguer, Francesc;Goel, Ajay
通讯作者：
Goel, Ajay
DOI：
10.1136/bmj.d4488
发表时间：
2011-08-26
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Buitrago-Lopez A;Sanderson J;Johnson L;Warnakula S;Wood A;Di Angelantonio E;Franco OH
通讯作者：
Franco OH
影响因子：
4.2
作者：
Day, JK;Bauer, AM;Lubahn, DB
通讯作者：
Lubahn, DB
影响因子：
8.8
作者：
Kato, K.;Long, N. K.;Makita, H.;Toida, M.;Yamashita, T.;Hatakeyama, D.;Hara, A.;Mori, H.;Shibata, T.
通讯作者：
Shibata, T.
影响因子：
3.6
作者：
Lee, WJ;Shim, JY;Zhu, BT
通讯作者：
Zhu, BT