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Review
. 2018 Feb;24(2):144-155.
doi: 10.1016/j.molmed.2017.12.003.

Aldehyde-Induced DNA and Protein Adducts as Biomarker Tools for Alcohol Use Disorder

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Free PMC article
Review

Aldehyde-Induced DNA and Protein Adducts as Biomarker Tools for Alcohol Use Disorder

Helen M Heymann et al. Trends Mol Med. .
Free PMC article

Abstract

Alcohol use disorder (AUD) screening frequently involves questionnaires complemented by laboratory work to monitor alcohol use and/or evaluate AUD-associated complications. Here we suggest that measuring aldehyde-induced DNA and protein adducts produced during alcohol metabolism may lead to earlier detection of AUD and AUD-associated complications compared with existing biomarkers. Use of aldehyde-induced adducts to monitor AUD may also be important when considering that approximately 540 million people bear a genetic variant of aldehyde dehydrogenase 2 (ALDH2) predisposing this population to aldehyde-induced toxicity with alcohol use. We posit that measuring aldehyde-induced adducts may provide a means to improve precision medicine approaches, taking into account lifestyle choices and genetics to evaluate AUD and AUD-associated complications.

Keywords: 4-hydroxynonenal; ALDH2; ALDH2*2; acetaldehyde; alcohol; alcohol use disorder; biomarker; reactive aldehydes.

Figures

Figure 1
Figure 1. Proposed Scheme to incorporate the measurement of aldehyde-induced adducts in clinical practice
Following a positive verbal screen, we propose practitioners can formally diagnose AUD using both criteria outlined in the DSM-V (which includes meeting two of 11 DSM-V criteria) and measurement of aldehyde-induced adducts. Aldehyde-induced protein and DNA adducts can be collected by a blood sample, saliva sample, or a cheek swab, and the sample can be analyzed by mass spectroscopy or an immunoassay such as ELISA for quantification. Adhering to current patient guidelines, standard biomarkers of alcohol use, including AST, ALT, GGT, CDT, and red blood cell MCV may be tested concurrently. ALT = alanine aminotransferase, AST = aspartate aminotransferase, AUDIT = Alcohol Use Disorders Identification Test, CDT = carbohydrate deficient transferrin, ELISA = enzyme-linked immunosorbent assay, GGT = gamma-glutamyl transferase, MCV = mean corpuscular volume.
Figure 2
Figure 2. Production of aldehyde-induced adducts following alcohol consumption in humans
The enzyme alcohol dehydrogenase converts ethanol to the highly reactive intermediate acetaldehyde. Acetaldehyde is then converted by aldehyde dehydrogenase 2 to the nontoxic molecule acetate. Alternatively, CYP2E1 metabolizes alcohol when ADH is saturated and is induced by chronic alcohol consumption. Acetaldehyde is highly reactive and can form complexes with protein or DNA known as adducts. CYP2E1 also generates acetaldehyde from ethanol, and its induction is a major source of oxygen radicals that can react with lipids in the cell to form the reactive aldehydes 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). 4-HNE and MDA also lead to DNA and protein adducts. Acetaldehyde, 4-HNE, and MDA can easily diffuse through cell membranes, forming aldehyde-induced adducts in the blood or other tissues.

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