Genomic DNA methylation decreases in response to moderate folate depletion in elderly women.
Genomic DNA methylation decreases in response to moderate folate depletion in elderly women.
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DOI：
10.1093/ajcn/72.4.998
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发表时间：
2000-10
期刊：
影响因子：
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通讯作者：
G. C. Rampersaud;G. Kauwell;A. Hutson;J. Cerda;L. Bailey
中科院分区：
文献类型：
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作者：
G. C. Rampersaud;G. Kauwell;A. Hutson;J. Cerda;L. Bailey
背景基因组DNA的甲基化依赖于叶酸辅酶的充足供应。以前的数据支持这一假设，即异常的DNA甲基化在癌症发生中起着不可或缺的作用。到目前为止，还没有研究评估叶酸不足对老年妇女（年龄>63岁）DNA甲基化的影响。目的探讨老年妇女（60-85岁）叶酸补充后的中度叶酸耗竭对白细胞基因组DNA甲基化的影响，以评价DNA甲基化是否可作为叶酸状态的功能指标。设计健康的绝经后妇女（n = 33）食用中度叶酸耗竭饮食（118微克叶酸/天）7周，随后7周的叶酸补充200或415微克/天，每个提供2种不同的饮食治疗，共4个治疗组（n = 30）。在体外试验中，根据DNA掺入标记S：-腺苷甲硫氨酸中[（3）H]甲基的能力，测定白细胞DNA甲基化。结果叶酸耗竭后[3 H]甲基的掺入显著增加（P = 0.0025），提示DNA甲基化不足。与消耗后值相比，在7周的补充期内，任何组的[（3）H]甲基掺入量均未检测到显著变化。结论：DNA甲基化状态可作为叶酸中度缺乏状态的功能性指标。观察到的对饱腹饮食的缓慢反应表明，在中度叶酸耗竭后，老年妇女的DNA甲基化正常化可能会延迟。
BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes. Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis. To date, no studies assessing the effect of inadequate folate status on DNA methylation in older women (aged >63 y) have been reported. OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women (aged 60-85 y) to evaluate whether DNA methylation could be used as a functional indicator of folate status. DESIGN Healthy, postmenopausal women (n = 33) consumed a moderately folate-depleted diet (118 microg folate/d) for 7 wk, followed by 7 wk of folate repletion with 200 or 415 microg/d, each provided as 2 different dietary treatments for a total of 4 treatment groups (n = 30). Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay. RESULTS Incorporation of [(3)H]methyl groups increased significantly (P: = 0.0025) in response to folate depletion, suggesting undermethylation of DNA. No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values. CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status. The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women.