Project SummaryExcessive alcohol use (EAU) is one the leading causes of preventable injury and death in the Unites States.Timely intervention and effective treatment of EAU relies on early detection of excessive drinking, usuallythrough clinical screening. Delayed recognition of early signs and symptoms of EAU would lead to missedopportunities to interrupt the accumulation of alcohol exposure and result in suboptimal care outcomes inalcohol-related health conditions. There is an urgent need for increased vigilance and action to identify and tocounsel patients that are at-risk for EAU. Using human transcriptome along with proteomic approaches, wehave uncovered markers that are potentially linked to the EAU pathophysiology. We found that activationof monocytes by alcohol (sCd14, sCD163, and urine neopterin) and suppression of CD4+ follicular T cells(sCD40) are strongly associated with levels of alcohol consumption. We believe that with the aid of modernanalytical techniques, these novel biomarkers could be used as basis for a new mechanistic-basedscreening strategy that have significantly improved the diagnostic performance. To test this hypothesis,we will pursue the following aims: Specific Aim 1. To ascertain the diagnostic potential of these novel serumand urinary markers for EAU; Specific Aim 2. To construct a screening score that represents the EAUprobability of individual subject by using modern semiparametric regression techniques and markers identifiedin Aim#1; and Specific Aim 3. To validate the screening model. If successfully implemented, results from thisproject could revolutionize the practice of EAU screening and diagnosis. The identification of the novelmarkers also provides a scientific basis to better understand the mechanisms underlying the health sequelae ofEAU.
|Effective start/end date||8/10/16 → 7/31/21|
- National Institutes of Health: $342,183.00