Serum Proteomic Profiles as Biomarkers of Abusive Alcohol Consumption

描述（由申请人提供）： 过度饮酒被认为是一个新出现的与健康有关的问题，特别是在从战斗中返回的退伍军人中。有必要提高警惕并采取行动，以查明这些处境危险的退伍军人并为其提供咨询。不幸的是，我们缺乏可靠的诊断测试来检测饮酒的危险水平。这些测试对于筛查和照顾过度饮酒的退伍军人是必不可少的。我们假设，高水平的酒精消耗会激发细胞和分子反应，其后遗症通过血清中独特和低丰度蛋白质或蛋白质片段的出现或血清蛋白质糖基化状态的变化或两者而明显。这些分子可能来源于各种组织和细胞，与酒精诱导的肝损伤的常规/传统标志物无关。为了验证这一假设，我们计划追求以下具体目标。具体目标# 1.通过检测、鉴定和比较血清蛋白和载体蛋白结合肽、蛋白和蛋白片段的相对量，确定过量饮酒对血清蛋白质组的影响，并将其作为潜在的生物标志物进行评估。我们将确定血清蛋白质组中的差异与过度使用酒精和“非危险饮酒者”控制的主题，并确定“评估窗口”的酒精使用障碍的退伍军人进行酒精康复治疗的血清蛋白质组水平。具体目标#2.测定特定目标#1中患者血清中糖蛋白富集组分的蛋白糖基化状态。如果成功，该项目的结果将彻底改变过度饮酒退伍军人的筛查方法。

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.