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. ? ? ?
