Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
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DOI：
10.1136/gut.2004.054718
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发表时间：
2005-05-01
期刊：
影响因子：
24.5
通讯作者：
Sanders, TAB
中科院分区：
文献类型：
--
作者：
Pufulete, M;Al-Ghnaniem, R;Sanders, TAB
背景和目的：低叶酸摄入可导致基因组DNA低甲基化，并可能增加结直肠肿瘤的风险。叶酸补充剂增加白细胞和结直肠粘膜DNA甲基化的假设进行了测试，在31例组织学证实的结直肠腺瘤使用随机，双盲，安慰剂对照，平行design.Methods：受试者随机接受400 μ g/天叶酸补充剂（n = 15）或安慰剂（n = 16）为10周。在基线和干预后测定基因组DNA甲基化、血清和红细胞叶酸以及血浆同型半胱氨酸浓度。结果：补充叶酸使血清和红细胞叶酸浓度增加81%（95%置信区间（CI）57-104%; p < 0.001，与安慰剂相比）和57%（95% CI 40-74%; p < 0.001，与安慰剂相比），血浆同型半胱氨酸浓度降低12%（95% CI 4-20%; p = 0.01，与安慰剂相比）。补充叶酸导致白细胞DNA甲基化增加31%（95%CI 16-47%; p = 0.05 v安慰剂），结肠粘膜DNA甲基化增加25%（95%CI 11-39%; p = 0.09 v安慰剂）。
Background and aims: A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design.Methods: Subjects were randomised to receive either 400 mu g/day folic acid supplement (n = 15) or placebo (n = 16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention.Results: Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57-104%; p < 0.001 v placebo) and 57% (95% CI 40-74%; p < 0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4-20%; p = 0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16-47%; p = 0.05 v placebo) in leucocytes and 25% (95% CI 11-39%; p = 0.09 v placebo) in colonic mucosa.Conclusions: These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.