Metabolomic biomarkers of daily alcohol intake and alcohol-induced hepatopathy in community-dwelling adults: Tsuruoka Metabolomic Cohort Study, Japan

Monday, 18 August 2014: 11:00 AM
Ballroom D (Dena'ina Center)
Sei Harada, MD , Keio University, Tokyo, Japan
Toru Takebayashi, MD , Keio University, Tokyo, Japan
Ayako Kurihara, MS , Keio University, Tokyo, Japan
Tomonori Okamura, MD , Keio University, Tokyo, Japan
Daisuke Sugiyama, MD , Keio University, Tokyo, Japan
Ayano Takeuchi, PhD , National Institute for Environmental Studies, Tsukuba, Japan
Akiyoshi Hirayama, PhD , Keio University, Tsuruoka, Japan
Masahiro Sugimoto, PhD , Keio University, Tsuruoka, Japan
Tomoyoshi Soga, PhD , Keio University, Tsuruoka, Japan
Masaru Tomita, PhD , Keio University, Tsuruoka, Japan
INTRODUCTION: We started a cohort study in Tsuruoka City from 2012, and performed the capillary electrophoresis–mass spectrometry (CE/MS) metabolome profiling on the 2,136 plasma samples of Japanese.  Our aim is to examine the metabolic status of healthy people and to identify early pathophysiological changes which can predict development of lifestyle-related diseases.  In this paper, our special interest is to describe how daily alcohol intake affects plasma metabolome, and to determine the metabolomic biomarkers associated with development of alcoholic hepatopathy.

METHODS: Subjects are 35 to 74 years-old residents enrolled into a longitudinal cohort study in Tsuruoka City from April to July 2012, as a part of three-year baseline.  896 Japanese men were included to the final analysis set (women were excluded because of the low alcohol intake).  115 polar metabolites were identified and absolutely quantified by CE/MS; amino acids, amines, organic acids, purines and the others.  Daily alcohol consumption was estimated by the detailed questionnaire.  665 men (74.2%) were classified to current drinkers (>1g ethanol per day).  To examine the association between the daily alcohol intake groups (none, low, middle and high alcohol intake) and each metabolite, we conducted the analysis of variance and calculated trend p-values adjusted for Benjamini and Hochberg's false discovery rate (FDR) method (α=0.05).  We also performed the regression analysis between alcohol-related metabolites on the serum AST, ALT, gamma-GTP levels among the highest tertile of the daily alcohol consumption to determine the metabolomics biomarkers associated with alcoholic hepatopathy, adjusted by considerable confounding.

RESULTS: Median of alcohol consumption was 35.7 g/day. 33 metabolites were significantly related to alcohol consumption, 2-aminobutyrate and pipecolate particularly showing low p values.  Among these 33 metabolites, glutamine, threonine and malate were significantly related to the serum AST, ALT, gamma-GTP levels.  In addition, we found that the glutamate/glutamine ratio had quite stronger association.

CONCLUSIONS: We found 33 polar metabolites related to daily alcohol consumption in community dwelling men, applying the metabolomics method to the large population-based study.  The glutamate/glutamine ratio may be a good biomarker of alcoholic hepatopathy.

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