Glahn Alexander, Rhein Mathias, Heberlein Annemarie, Muschler Marc, Kornhuber Johannes, Frieling Helge, Bleich Stefan, Hillemacher Thomas
Center for Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
Neuropsychobiology. 2016;74(3):131-138. doi: 10.1159/000456011. Epub 2017 Apr 26.
Natriuretic peptides participate in the collection of metabolic effects during alcohol withdrawal. Having witnessed modulation of other natriuretic peptides in alcohol-dependent patients during alcohol withdrawal, we were interested in the relation of brain natriuretic peptide (BNP) methylation with protein expression and craving in this longitudinal study.
Ninety-nine male patients were compared to 101 healthy controls concerning epigenetic regulation and protein expression during detoxification treatment.
With BNP expression being GATA4 dependent, we observed a correlation of GATA4 binding site methylation and protein expression. BNP serum levels and Obsessive Compulsive Drinking Scale scores are significantly decreased during withdrawal. Focusing on the two CpGs that are between GATA transcription factor binding sites, statistical analysis revealed a reversely proportional methylation pattern, significantly increasing with ongoing detoxification and thereby supporting the observed serum level changes.
Without the functional knowledge about regulation of BNP expression via the GATA transcription factor, it would have been easy to take the mean results of the global CpG data and propose a direct relationship between methylation and expression. Thus, these findings are a voice for functionally and mechanistically approved results. There was no causal relationship between protein expression levels and epigenetic changes. Further research is needed which includes protein expression and other approaches.
利钠肽参与酒精戒断期间的代谢效应。鉴于已观察到酒精依赖患者在酒精戒断期间其他利钠肽的调节情况，我们在这项纵向研究中对脑利钠肽（BNP）甲基化与蛋白表达及渴望之间的关系感兴趣。
将99名男性患者与101名健康对照者在解毒治疗期间的表观遗传调控和蛋白表达情况进行比较。
由于BNP表达依赖于GATA4，我们观察到GATA4结合位点甲基化与蛋白表达之间存在相关性。戒断期间BNP血清水平和强迫性饮酒量表评分显著降低。聚焦于GATA转录因子结合位点之间的两个CpG，统计分析显示出一种反比例甲基化模式，随着解毒过程的进行显著增加，从而支持了观察到的血清水平变化。
如果不了解通过GATA转录因子调节BNP表达的功能知识，很容易采用全局CpG数据的平均结果并提出甲基化与表达之间的直接关系。因此，这些发现为功能和机制上得到认可的结果提供了依据。蛋白表达水平与表观遗传变化之间不存在因果关系。需要进一步开展包括蛋白表达及其他方法的研究。
