Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.
Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.
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DOI：
10.1007/s12199-015-0494-y
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发表时间：
2016-01
影响因子：
4.7
通讯作者：
Tomita M
中科院分区：
文献类型：
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作者：
Harada S;Takebayashi T;Kurihara A;Akiyama M;Suzuki A;Hatakeyama Y;Sugiyama D;Kuwabara K;Takeuchi A;Okamura T;Nishiwaki Y;Tanaka T;Hirayama A;Sugimoto M;Soga T;Tomita M
代谢组学是鉴定血浆中生物标志物的一种很有前途的方法。在这里，我们进行了一项基于人群的横断面研究，通过使用毛细管电泳质谱(CE-MS)进行代谢组谱分析，以确定酒精摄入和酒精诱导的肝损伤的潜在生物标志物。采集了参加Tsuruoka代谢组学队列研究基线调查的896名日本男性的空腹血浆样本，用CE-MS鉴定并绝对定量了115种极性代谢物。有关每日酒精摄入量的信息是通过标准化的自填式问卷收集的。研究了酒精摄入量与血浆代谢物浓度之间的关系。然后用线性回归分析检验最高酒精摄入量组(>；46.0g/d)的代谢物浓度或代谢物比例与血清肝酶水平之间的关系。对从该队列的独立人群中收集的193个样本进行了复制分析。在原始和复制人群中，19种代谢物被鉴定为与日常饮酒有关。这些代谢物中的三种(苏氨酸、谷氨酰胺和琥珀酸胍)被发现与最高酒精摄入量组的血清肝酶水平升高有很好的相关性，但在不饮酒组中则不是。我们还发现，谷氨酸/谷氨酰胺比值与血清γ-谷氨酰转氨酶、天冬氨酸转氨酶和丙氨酸转氨酶的关系比谷氨酸或谷氨酰胺单独作用强得多(标准化β系数分别为0.678、0.558、0.498)。我们发现了19种与酒精摄入有关的代谢物，以及三种酒精肝损伤的候选生物标志物(苏氨酸、琥珀酸胍和谷氨酰胺)。谷氨酸/谷氨酰胺比值也可能是较好的生物标志物。本文的在线版本(doi：10.1007/s121990150494-y)包含补充材料，授权用户可以使用。
Metabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS). Fasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort. Nineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively). We found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker. The online version of this article (doi:10.1007/s12199-015-0494-y) contains supplementary material, which is available to authorized users.