Serum Proteomic Profiles as Biomarkers of Abusive Alcohol Consumption

描述(由申请人提供)： 过度饮酒正被认为是一个新出现的与健康有关的问题，特别是在从战斗中归来的退伍军人中。有必要提高警惕和采取行动，以识别和咨询这些处于危险之中的退伍军人。不幸的是，我们缺乏可靠的诊断测试来检测饮酒的危险程度。对于过度饮酒的退伍军人的筛查和护理来说，这样的测试是不可或缺的。我们假设，高水平的饮酒会引起细胞和分子反应，其后遗症是通过血清中出现独特的低丰度蛋白质或蛋白质片段，或改变血清蛋白质的糖基化状态，或两者兼而有之。这些分子可能来自多种组织和细胞，与酒精性肝损伤的常规/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。通过检测、鉴定和比较血清蛋白质和载体蛋白结合肽、蛋白质和蛋白质片段的相对数量，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。我们将确定过度饮酒受试者和非危险饮酒者对照组血清蛋白质组的差异，并确定接受酒精康复治疗的退伍军人酒精使用障碍患者血清蛋白质组水平的评估窗口。特定目的#2.确定从特定目的#1患者的血清中获得的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退伍军人过度饮酒的筛查方法。

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.