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Alcohol-induced metabolomic differences in humans

机译:酒精引起的人体代谢组学差异

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摘要

Alcohol consumption is one of the world's major risk factors for disease development. But underlying mechanisms by which moderate-to-heavy alcohol intake causes damage are poorly understood and biomarkers are sub-optimal. Here, we investigated metabolite concentration differences in relation to alcohol intake in 2090 individuals of the KORA F4 and replicated results in 261 KORA F3 and up to 629 females of the TwinsUK adult bioresource. Using logistic regression analysis adjusted for age, body mass index, smoking, high-density lipoproteins and triglycerides, we identified 40/18 significant metabolites in males/females with P-values <3.8E−04 (Bonferroni corrected) that differed in concentrations between moderate-to-heavy drinkers (MHD) and light drinkers (LD) in the KORA F4 study. We further identified specific profiles of the 10/5 metabolites in males/females that clearly separated LD from MHD in the KORA F4 cohort. For those metabolites, the respective area under the receiver operating characteristic curves were 0.812/0.679, respectively, thus providing moderate-to-high sensitivity and specificity for the discrimination of LD to MHD. A number of alcohol-related metabolites could be replicated in the KORA F3 and TwinsUK studies. Our data suggests that metabolomic profiles based on diacylphosphatidylcholines, lysophosphatidylcholines, ether lipids and sphingolipids form a new class of biomarkers for excess alcohol intake and have potential for future epidemiological and clinical studies.
机译:饮酒是世界上疾病发展的主要危险因素之一。但是,人们对中度至重度饮酒导致损害的潜在机制了解甚少,而且生物标志物不是最理想的。在这里,我们调查了2090例KORA F4个体中与酒精摄入相关的代谢物浓度差异,并在261 KORA F3和TwinsUK成人生物资源中的629名女性中复制了结果。使用针对年龄,体重指数,吸烟,高密度脂蛋白和甘油三酸酯校正的逻辑回归分析,我们确定了男性/女性中40/18个重要代谢物,其P值<3.8E-04(经Bonferroni校正)之间的浓度不同KORA F4研究中的中度至重度饮酒者(MHD)和轻度饮酒者(LD)。我们进一步确定了在男性/女性中10/5代谢物的特定特征,这些特征清楚地将KORA F4队列中的LD与MHD分开。对于这些代谢物,受体工作特性曲线下的各自面积分别为0.812 / 0.679,因此为LD到MHD的鉴别提供了中到高的灵敏度和特异性。 KORA F3和TwinsUK研究中可以复制许多与酒精有关的代谢物。我们的数据表明,基于二酰基磷脂酰胆碱,溶血磷脂酰胆碱,醚类脂和鞘脂的代谢组学谱形成了过量摄入酒精的新型生物标志物,并有可能用于未来的流行病学和临床研究。

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