title: Metabolic phenotyping of urine for discriminating alcohol-dependent from social drinkers and alcohol-naive subjects.
abstract: Alcohol-dependence (AD) is a ravaging public health and social problem. AD diagnosis depends on questionnaires and some biomarkers, which lack specificity and sensitivity, however, often leading to less precise diagnosis, as well as delaying treatment. This represents a great burden, not only on AD individuals but also on their families. Metabolomics using nuclear magnetic resonance spectroscopy (NMR) can provide novel techniques for the identification of novel biomarkers of AD. These putative biomarkers can facilitate early diagnosis of AD.
  
  
  
  To identify novel biomarkers able to discriminate between alcohol-dependent, non-AD alcohol drinkers and controls using metabolomics.
  
  
  
  Urine samples were collected from 30 alcohol-dependent persons who did not yet start AD treatment, 54 social drinkers and 60 controls, who were then analysed using NMR. Data analysis was done using multivariate analysis including principal component analysis (PCA) and orthogonal partial least square-discriminate analysis (OPLS-DA), followed by univariate and multivariate logistic regression to develop the discriminatory model. The reproducibility was done using intraclass correlation coefficient (ICC).
  
  
  
  The OPLS-DA revealed significant discrimination between AD and other groups with sensitivity 86.21%, specificity 97.25% and accuracy 94.93%. Six biomarkers were significantly associated with AD in the multivariate logistic regression model. These biomarkers were cis-aconitic acid, citric acid, alanine, lactic acid, 1,2-propanediol and 2-hydroxyisovaleric acid. The reproducibility of all biomarkers was excellent (0.81-1.0).
  
  
  
  This study revealed that metabolomics analysis of urine using NMR identified AD novel biomarkers which can discriminate AD from social drinkers and controls with high accuracy.
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Malaysia.
authors: Hamza
authors: H
authors: Mostafa
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Malaysia.
authors: Arwa M
authors: AM
authors: Amin
authors: Bruker Sdn Bhd, Malaysia.
authors: Chin-Hoe
authors: CH
authors: Teh
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Malaysia.
authors: Vikneswaran
authors: V
authors: Murugaiyah
authors: Psychiatry Department, Hospital Pulau Pinang, Malaysia.
authors: Nor Hayati
authors: NH
authors: Arif
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Malaysia. Electronic address: baharudin.ibrahim@usm.my.
authors: Baharudin
authors: B
authors: Ibrahim
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000652:urine*; D000437:Alcoholism / Q000175:diagnosis / Q000453:epidemiology* / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010641:Phenotype; D015203:Reproducibility of Results; D014631:Valerates / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014631:Valerates; C035864:2-hydroxyisovaleric acid
keywords: Alcohol-dependence; Biomarker; Metabolomics; Nuclear magnetic resonance; Urine