title: Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.
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.
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.|Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. ttakebayashi@a3.keio.jp.|Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan. ttakebayashi@a3.keio.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Takebayashi
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.|Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurihara
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.|Faculty of Environment and Information Studies, Keio University, Fujisawa, 252-0882, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Akiyama
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hatakeyama
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Kuwabara
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Division of Environmental and Occupational Health, Department of Social Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, 143-0015, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiwaki
authors.affiliation: Division of Environmental and Occupational Health, Department of Social Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, 143-0015, Japan.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirayama
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.|Faculty of Environment and Information Studies, Keio University, Fujisawa, 252-0882, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan.|Faculty of Environment and Information Studies, Keio University, Fujisawa, 252-0882, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000097:blood / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D008875:Middle Aged
chemical_list: D015415:Biomarkers
keywords: Alcohol; Alcoholic liver disease; Amino acids; Biomarker; Metabolomics