Serum Proteomic Profiles as Biomarkers of Abusive Alcohol Consumption

Rlr Va Medical Center, Indianapolis IN

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Abstract

DESCRIPTION (provided by applicant): Excessive alcohol use is becoming recognized as an emerging health-related problem especially among veterans returning from combats. There is a need for increased vigilance and action to identify and counsel these at-risk veterans. Unfortunately, we lack the reliable diagnostic tests to detect the dangerous levels of drinking. Such tests would be indispensable for screening and care for veterans with excessive alcohol use. We hypothesize that alcohol consumption at high levels elicits cellular and molecular responses whose sequelae are apparent through the appearance of unique and low- abundance proteins or protein fragments in the serum, or changes in the glycosylation status of serum proteins, or both. These molecules may be derived from a variety of tissues and cells and are unrelated to conventional/traditional markers of alcohol-induced liver injury. To test this hypothesis, we plan to pursue the following specific aims. SPECIFIC AIM # 1. Determine the effect of excessive alcohol drinking on the serum proteome by detecting, identifying, and comparing the relative quantity of serum proteins and carrier protein-bound peptides, proteins, and protein fragments and evaluate these as potential biomarkers. We will determine the difference in serum proteomes in subjects with excessive use of alcohol and 'non-risky drinker' controls and determine the 'window of assessment' of the levels of serum proteomes in veterans with alcohol use disorder undertaking alcohol rehabilitation treatment. SPECIFIC AIM # 2. Determine the protein glycosylation status of glycoprotein enriched fractions from sera obtained from the patients in Specific Aim #1. If successful, the results from this project will revolutionize the screening methods for veterans with excessive alcohol use.