PDF(Pubmed)
Abstract：
Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10-5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.
摘要：
目前,临床医生使用他们的判断和指标，如酒精戒断综合征预测量表（PAWSS），以确定患者是否入院考虑戒断综合征（AWS）。然而,只有一小部分被录取的人会经历严重的AWS。以前,我们和其他人已经证明了表观遗传指数，如酒精T评分(ATS)，可以量化最近的酒精消费。然而,无论是这些或其他酒精生物标志物，如碳水化合物缺乏转铁蛋白（CDT），无法识别有严重AWS风险的人是未知的。为了确定这一点，我们首先对进入和退出酒精治疗的受试者进行了全基因组DNA甲基化分析,以确定其甲基化随着禁欲而迅速恢复的基因座.然后我们测试了快速回复位点的甲基化是否，cg07375256，或其他现有指标，包括PAWSS分数，CDT水平,或者ATS,可以预测125名考虑AWS的受试者的结果。我们发现，PAWSS并不能显著预测严重的AWS或癫痫发作。然而,cg07375256（ZSCAN25）和CDT的甲基化强烈预测严重的AWS与ATS（p<0.007）和cg07375256（p<6×10-5）甲基化也预测AWS相关的癫痫发作。我们得出的结论是，表观遗传方法可以预测那些可能经历严重AWS的人，并且使用这些或类似的Precision表观遗传方法可以更好地指导AWS管理。
