title: Novel serum biomarkers for detection of excessive alcohol use.
abstract: BACKGROUND
  Construct interview that correctly identifies those with alcohol use disorder have limitation, especially when the subjects are motivated to minimize the magnitude of drinking behavior. Current laboratory tests to detect excessive alcohol consumption are limited by marginal sensitivity/specificity. Excessive drinking has been shown to affect several organ systems, which may be reflected in changes in quantity of plasma proteins. Our aim was to employ novel proteomic analyses to identify potential markers for excessive alcohol use.
  
  
  METHODS
  A prospective case-control study included 49 controls and 54 excessive drinkers (discovery cohort). The serum proteomic analyses in these subjects were performed, and the results were tested in the verification cohort (40 controls and 40 excessive drinkers).
  
  
  RESULTS
  Using the appropriate cutoff and confirmation with ELISA, we identified 4 proteins which were significantly elevated in the serum of excessive drinkers: AT-rich interactive domain-containing protein 4B (ARID4B), phosphatidylcholine-sterol acyltransferase (LCAT), hepatocyte growth factor-like protein (MST1), and ADP-ribosylation factor 6 (ARL6). The performance of the conventional markers (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [GGT], percentage of carbohydrate-deficient transferrin [%CDT], and mean corpuscular volume [MCV]) discriminating between excessive alcohol use and controls had an area under the curve (AUC) ranging from 0.21 (ALT) to 0.67 (MCV). The AUC of these novel proteins showed the improvement in the detection of excessive drinkers compared to conventional laboratory tests, ranging from 0.73 (for ARID4B) to 0.86 (for ARL6).
  
  
  CONCLUSIONS
  We have identified 4 novel proteins that can discern subjects with excessive alcohol use. Further studies are needed to determine the clinical implications of these markers to detect excessive alcohol use and confirm abstinence.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Roudebush Veterans Administration Medical Center, Indianapolis, Indiana.
authors.forename: Suthat
authors.initials: S
authors.lastname: Liangpunsakul
authors.forename: Xianyin
authors.initials: X
authors.lastname: Lai
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Ross
authors.forename: Zhangsheng
authors.initials: Z
authors.lastname: Yu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Modlik
authors.forename: Chi
authors.initials: C
authors.lastname: Westerhold
authors.forename: Laura
authors.initials: L
authors.lastname: Heathers
authors.forename: Robin
authors.initials: R
authors.lastname: Paul
authors.forename: Sean
authors.initials: S
authors.lastname: O'Connor
authors.forename: David W
authors.initials: DW
authors.lastname: Crabb
authors.forename: Frank
authors.initials: F
authors.lastname: Witzmann
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000097:blood*; D000328:Adult; D019973:Alcohol-Related Disorders / Q000097:blood* / Q000175:diagnosis*; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*
chemical_list: D000089982:ADP-Ribosylation Factor 6; C493892:ARID4B protein, human; D000951:Antigens, Neoplasm; D015415:Biomarkers; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; C491435:ARL6 protein, human; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human
keywords: Excessive Alcohol Use; LC/MS; Proteomics; Serum Markers