Protein Biomarker Profiles:Abusive Alcohol Consumption

蛋白质生物标志物概况：滥用酒精消费

• 批准号: 7085736
• 负责人: Frank A Witzmann
• 金额: $ 21.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085736
• 关键词: albumins; alcoholic beverage consumption; alcoholism /alcohol abuse; biomarker; blood proteins; blood tests; body composition; clinical research; drug /alcohol abstinence; gender difference; human subject; mass spectrometry; patient oriented research; pharmacokinetics; plasma; proteomics; questionnaires; racial /ethnic difference; albumins; alcoholic beverage consumption; alcoholism /alcohol abuse; biomarker; blood proteins; blood tests; body composition; clinical research; drug /alcohol abstinence; gender difference; human subject; mass spectrometry; patient oriented research; pharmacokinetics; plasma; proteomics; questionnaires; racial /ethnic difference

DESCRIPTION (provided by applicant): The long-term objective of this project is to detect a novel biomarker (or confined set of biomarkers) of heavy/abusive alcohol consumption in the plasma of human subjects. The working hypothesis for this aim is that alcohol consumption at high levels elicits cellular and molecular responses whose sequelae are manifest through the appearance of unique and low-abundance polypeptides or proteins in the plasma. These molecules may be derived from a variety of tissues and cells and are unrelated to conventional/traditional markers of alcohol-induced liver injury. We hypothesize that low abundance peptide and low molecular weight protein biomarkers are to be found complexed with high-abundance plasma proteins such as albumin. Our strategy is to preferentially recover these potential biomarkers by plasma albumin affinitycapture, elute and concentrate them, and then acquire whole peptide/protein mass spectra of the mixture. Raw spectral data will then be analyzed, comparing control plasma with samples from alcohol drinkers, and drinkers during early abstinence. Diagnostic peptide/protein patterns will be sought based on various patient classifications. In this regard, our specific aims are to: 1) determine the effect of a defined exposure to alcohol in normal individuals on the plasma proteome, using alcohol clamping to minimize the between-individual variation in alcohol absorption and pharmacokinetics; 2) determine the effect of sustained abusive drinking on the plasma proteome. The subjects will be recruited from patients seeking treatment for alcohol abuse and dependence, and plasma will be sampled at beginning and end of a 6 week intensive outpatient treatment; and 3) determine which proteomic signatures are influenced by patient characteristics such as body mass index, gender, ethnicity, and minor liver test abnormalities.

描述（由申请人提供）：该项目的长期目标是检测人类受试者血浆中重/滥用饮酒的新型生物标志物（或生物标志物的限制集）。此目的的工作假设是，高水平的饮酒会引起细胞和分子反应，其后遗症通过出现在血浆中的独特和低增强多肽或蛋白质而表现出来。这些分子可能来自多种组织和细胞，与酒精诱导的肝损伤的常规/传统标记无关。我们假设应发现低丰度肽和低分子量蛋白生物标志物与高丰度血浆蛋白（如白蛋白）复合。我们的策略是通过等离子体白蛋白亲和力，洗脱和浓缩它们，优先恢复这些潜在的生物标志物，然后获得混合物的整个肽/蛋白质质量光谱。 然后将分析原始光谱数据，将控制血浆与酒精饮用者的样品和饮酒者的样品进行比较。根据各种患者分类，将寻求诊断肽/蛋白质模式。在这方面，我们的具体目的是：1）确定正常个体对血浆蛋白质组的饮酒的影响，使用酒精夹紧来最大程度地减少酒精吸收和药代动力学的个体间变化； 2）确定持续滥用饮用对等离子体蛋白质组的影响。这些受试者将是从寻求酗酒和依赖治疗的患者中招募的，并且在6周强化门诊治疗的开始和结束时，血浆将进行采样； 3）确定哪些蛋白质组学特征受患者特征的影响，例如体重指数，性别，种族和小肝检测异常。