ABSTRACT

Currently, the most commonly used biomarker of alcohol consumption patterns is carbohydrate-deficient transferrin (CDT). However, the CDT has limited sensitivity and requires the use of blood. Recently, we have shown that digital DNA methylation techniques can both sensitively and specifically detect heavy alcohol consumption (HAC) using DNA from blood or saliva. In order to better understand the relative performance characteristics of these two tests, we compared an Alcohol T-Score (ATS) derived from our prior study and serum CDT levels in 313 (182 controls and 131 HAC cases) subjects discordant for HAC. Overall, the Receiver Operating Characteristic (ROC) area under the curve (AUC) analyses showed that DNA methylation predicted HAC status better than CDT with AUCs of 0.96 and 0.87, respectively (p < 0.0001). The performance of the CDT was affected by gender while the ATS was not, while both were affected by age. We conclude that DNA methylation is a promising method for quantifying HAC and that further studies to better refine its strengths and limitations are in order.

摘要

目前，酒精消费模式最常用的生物标志物是碳水化合物缺乏转铁蛋白 (CDT)。然而，CDT 的敏感性有限，需要使用血液。最近，我们已经证明，数字 DNA 甲基化技术可以使用血液或唾液中的 DNA 敏感和特异性地检测重度酒精消耗 (HAC)。为了更好地了解这两个测试的相对性能特征，我们比较了来自我们先前研究的酒精 T 评分 (ATS) 和 313 名（182 名对照和 131 名 HAC 病例）与 HAC 不一致的受试者的血清 CDT 水平。总体而言，接受者操作特征 (ROC) 曲线下面积 (AUC) 分析显示，DNA 甲基化预测 HAC 状态优于 CDT，AUC 分别为 0.96 和 0.87 (p < 0.0001)。CDT 的表现受性别影响，而 ATS 则不受性别影响，而两者都受年龄影响。我们得出结论，DNA 甲基化是量化 HAC 的一种有前途的方法，并且进一步研究以更好地改进其优势和局限性是有序的。