Modifications of glycated Hb:Novel biomarkers of alcohol

糖化血红蛋白的修饰：酒精的新型生物标志物

• 批准号: 7083271
• 负责人: YOUSEF AL-ABED
• 金额: $ 19.59万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7083271
• 关键词: acetaldehyde; adduct; alcoholic beverage consumption; alcoholism /alcohol abuse; antigens; behavioral /social science research tag; biomarker; chemical synthesis; disease /disorder model; drug addiction; endoribonucleases; enzyme activity; enzyme linked immunosorbent assay; erythrocytes; glycation; hemoglobin As; immunoconjugates; immunologic assay /test; laboratory mouse; laboratory rabbit; laboratory rat; mass spectrometry; method development; nuclear magnetic resonance spectroscopy; plasma; substance abuse related behavior

DESCRIPTION (provided by applicant): Chronic and binge drinking affect millions of Americans each year. A recent study revealed that alcohol contributes to 4% of the global burden of disease which is equivalent to the world-wide impact of tobacco use and hypertension (Reviewed in Room et al, Lancer 2005). In addition, alcohol abuse is associated with heavy social and economic burdens (approximately $185B annually). Based on sensitivity and specificity, the most reliable screening techniques for alcohol abuse are self-reporting methods. Clearly, the major shortcoming of self-reporting alcohol use by abusers is under-reporting. Interestingly, no biomarkers of binge drinking are available. Our long-term goal is to develop reliable methods to detect acute and chronic alcohol abuse. Our central hypothesis is that two stable acetaldehyde-modified glycosylated hemoglobin (Hb) adducts are produced following (A) binge and (B) chronic drinking and these represent specific and abundant markers of (A) acute and (B) chronic alcohol abuse, respectively. Our preliminary data show that (a) acetaldehyde modifies glycosylated Hb to form stable adducts; (b) glycosylated HbAo represents approximately 20% of the total Hb in healthy persons (while glycosylated HbA1c represents 3-5%); and (c) two types of Hb-acetaldehyde adducts form depending on the length and concentration of alcohol metabolite exposure. Specific aims: We propose to (1) conjugate acetaldehyde adducts onto protein carriers (that represent adducts formed following binge and chronic drinking, respectively) for the development of specific antibodies and (2) develop specific and sensitive immunoassay methods for detecting these biomarkers in the red blood cells and serum/plasma using rat experimental models of acute/binge drinking or chronic alcohol administration, respectively. Relevance to public health: Alcohol abuse, including chronic alcohol abuse (or alcoholism) and binge drinking (defined as having equal to or >5 drinks on one occasion within the past month) is the third leading cause of preventable death in the US. Binge drinking has significantly increased in the past few years, affecting up to 39 out of 100 teens and young adults interviewed. Although alcohol treatment programs are successful for helping alcohol abusers, many alcohol abusers are not treated because we lack good methods for identifying alcohol abusers. Currently, self-reporting methods (questionnaires) are used to detect alcohol abuse because we do not have better procedures that reliably determine alcohol abuse using blood, saliva, or urine. Our early studies show that acetaldehyde (alcohol's breakdown product in the blood) binds to modified hemoglobin (the major protein found in red blood cells) following binge and chronic drinking to form two different 'markers.' We will develop specific methods for identifying binge and chronic alcohol-specific markers in the blood/red blood cells of rats administered acute or chronic alcohol. Future studies will be designed to measure these alcohol-specific-markers in humans following binge and chronic alcohol intake.

描述（由申请人提供）：慢性和酗酒每年影响数百万美国人。最近的一项研究表明，酒精占全球疾病负担的4%，相当于烟草使用和高血压的全球影响（见Room等人，Lancer， 2005年）。此外，酗酒还会带来沉重的社会和经济负担（每年约1850亿美元）。基于敏感性和特异性，最可靠的酒精滥用筛查技术是自我报告方法。显然，滥用者自我报告酒精使用情况的主要缺点是报告不足。有趣的是，目前还没有关于酗酒的生物标志物。我们的长期目标是开发可靠的方法来检测急性和慢性酒精滥用。