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Environ Health Prev Med. 2016 Jan;21(1):18-26. doi: 10.1007/s12199-015-0494-y. Epub 2015 Oct 12.

Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.

Author information

1
Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
2
Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
3
Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. ttakebayashi@a3.keio.jp.
4
Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan. ttakebayashi@a3.keio.jp.
5
Faculty of Environment and Information Studies, Keio University, Fujisawa, 252-0882, Japan.
6
Division of Environmental and Occupational Health, Department of Social Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, 143-0015, Japan.

Abstract

OBJECTIVE:

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).

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

KEYWORDS:

Alcohol; Alcoholic liver disease; Amino acids; Biomarker; Metabolomics

PMID:
26459263
PMCID:
PMC4693765
DOI:
10.1007/s12199-015-0494-y
[Indexed for MEDLINE]
Free PMC Article

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