Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism
Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism
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DOI：
10.1007/s00702-005-0413-2
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发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Bleich, S.
中科院分区：
文献类型：
--
作者：
Boensch, D.;Lenz, B.;Bleich, S.
DNA甲基转移酶（DNMT）参与DNA甲基化过程的表观遗传控制。最近，研究表明酒精中毒患者的基因组DNA甲基化水平升高。在本对照研究中，我们观察到酒精患者（n = 59）与健康对照（n = 66）相比，DNMT-3a和DNMT-3b的mRNA表达显著降低：DNMT-3a（t =-2.38，p = 0.019），DNMT-3b（t =-2.65，p = 0.008）。DNMT-1和Mbd-2（甲基CpG结合结构域蛋白2）表达无显著差异。此外，我们观察到DNMT-3b表达与血液酒精浓度之间存在显著负相关（r =-0.45，p = 0.003），这可能解释了酒精患者DNMT-3b mRNA表达的降低。使用多变量模型，我们观察到酒精中毒患者基因组DNA甲基化的增加（10%）与他们降低的DNMT-3b mRNA表达显著相关（多元线性回归，p = 0.014）。由于DNA甲基化是调节基因表达的重要表观遗传因素，这些发现可能对这些患者的表观遗传控制的可能后续紊乱具有重要意义。
DNA methyltransferases (DNMTs) are involved within the epigenetic control of DNA methylation processes. Recently, it has been shown that the genomic DNA methylation in patients with alcoholism is increased. In the present controlled study we observed a significant decrease of mRNA expression of DNMT-3a and DNMT-3b when comparing alcoholic patients (n = 59) with healthy controls (n = 66): DNMT-3a (t = -2.38, p = 0.019), DNMT-3b (t = -2.65, p = 0.008). No significant differences were seen for DNMT-1 and Mbd-2 (Methyl-CpG-Binding-Domain protein 2) expression. Additionally, we observed a significant negative correlation between DNMT-3b expression and the blood alcohol concentration (r = -0.45, p = 0.003) which might explain the decrease of DNMT-3b mRNA expression in alcoholic patients. Using a multivariate model we observed that the increase (10%) of genomic DNA methylation in patients with alcoholism was significantly associated with their lowered DNMT-3b mRNA expression (multiple linear regression, p = 0.014). Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have important implications for a possible subsequent derangement of epigenetic control in these patients.