Gene-nutrient interactions and DNA methylation
Gene-nutrient interactions and DNA methylation
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DOI：
10.1093/jn/132.8.2382s
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发表时间：
2002-08-01
影响因子：
4.2
通讯作者：
Choi, SW
中科院分区：
文献类型：
--
作者：
Friso, S;Choi, SW
许多微量营养素和维生素对DNA合成/修复和DNA甲基化模式的维持至关重要。由于叶酸作为核苷酸合成和生物甲基化的甲基供体的独特功能，叶酸在这方面得到了最广泛的研究。细胞培养以及动物和人类研究表明，叶酸缺乏会诱导DNA的破坏以及DNA甲基化状态的改变。甲基缺乏症的动物模型比单独使用叶酸缺乏症饮食的研究显示出更强的因果关系。这些观察结果表明，叶酸不足对DNA代谢的不利影响主要是由于甲基供应的损害。最近，在确定基因组DNA甲基化中，观察到叶酸状态与编码亚甲基四氢叶酸还原酶（一碳代谢中的必需酶）的基因中的常见突变之间的相互作用。这一发现表明，营养状况与遗传多态性之间的相互作用可以通过DNA甲基化调节基因表达，特别是当这种多态性限制甲基供应时。DNA甲基化，无论是全基因组还是基因特异性的，对于癌症、衰老和其他与细胞周期调控和组织特异性分化相关的疾病的研究都特别有意义，因为它会影响基因表达，而不会导致DNA序列的永久性改变，如突变或等位基因缺失。通过与营养物质的相互作用来了解DNA甲基化的模式是至关重要的，不仅可以为某些疾病的发展提供病理生理学解释，而且可以通过改变高危人群的营养状况来提高对可能的预防策略的认识。
Many micronutrients and vitamins are critical for DNA synthesis/repair and maintenance of DNA methylation patterns. Folate has been most extensively investigated in this regard because of its unique function as methyl donor for nucleotide synthesis and biological methylation. Cell culture and animal and human studies showed that deficiency of folate induces disruption of DNA as well as alterations in DNA methylation status. Animal models of methyl deficiency demonstrated an even stronger cause-and-effect relationship than did studies using a folate-deficient diet alone. Such observations imply that the adverse effects of inadequate folate status on DNA metabolism are mostly due to the impairment of methyl supply. Recently, an interaction was observed between folate status and a common mutation in the gene encoding for methylenetetrahydrofolate reductase, an essential enzyme in one-carbon metabolism, in determining genomic DNA methylation. This finding suggests that the interaction between a nutritional status with a genetic polymorphism can modulate gene expression through DNA methylation, especially when such polymorphism limits the methyl supply. DNA methylation, both genome-wide and gene-specific, is of particular interest for the study of cancer, aging and other conditions related to cell-cycle regulation and tissue-specific differentiation, because it affects gene expression without permanent alterations in DNA sequence such as mutations or allele deletions. Understanding the patterns of DNA methylation through the interaction with nutrients is fundamental, not only to provide pathophysiological explanations for the development of certain diseases, but also to improve the knowledge of possible prevention strategies by modifying a nutritional status in at-risk populations.