Genetics of Alcohol Metabolism

Abstract

Key PointsAlcohol metabolism occurs mainly via hepatic oxidation and is governed by the catalytic properties • of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH2). Genetic polymorphisms in • ADH1B and ALDH2 , and ethnic differences in the prevalence of these polymorphisms, result in increased variation in alcohol metabolism among individuals. Polymorphisms in • ADH1B result in variants that code for isozymes that tend to show a faster rate of alcohol metabolism, while the ALDH2*2 polymorphism results in a "de fi cient" form of ALDH2 that causes an accumulation of acetaldehyde and its associated physiological effects.• ADH and ALDH polymorphisms are also associated with a protective effect on the development of alcoholism. The allele frequencies of ADH1B*2 , ADH1B*3 , and ALDH2*2 are signi fi cantly lower in individuals diagnosed with alcohol dependence compared to controls. Further evaluation of the factors, both genetic and environmental, regulating the rates of alcohol • and acetaldehyde metabolism, will help improve our understanding of the metabolic basis and consequences of alcohol's effects, including the risk and consequences of alcohol-related organ damage, developmental problems, as well as alcohol dependence.

Site of Alcohol First-Pass Metabolism Among Women

“…For the clamp, an IV catheter was inserted into the antecubital vein to infuse 6%v/v alcohol in half-normal saline. Using the computer-assisted alcohol infusion system, a target breath alcohol concentration of 60 mg/dL was achieved at 15 minutes and maintained for 135 minutes. AER was estimated from the steady state portion of the last 40 minutes of the clamp .…”

“…Using the computer-assisted alcohol infusion system, a target breath alcohol concentration of 60 mg/dL was achieved at 15 minutes and maintained for 135 minutes. AER was estimated from the steady state portion of the last 40 minutes of the clamp . We used analyses of variance and Kruskal-Wallis test to compare pharmacokinetic parameters and other outcomes between groups (eMethods in the Supplement).…”

“…This design allowed differentiation of the effects of gastric emptying rate on hepatic vs gastric FPM. In addition, to control for association of SG with potential changes in systemic alcohol elimination rates (AER) that could confound differences in the bioavailability of ingested alcohol between groups, we used an intravenous (IV) alcohol clamp that estimates AER independent of variations in alcohol absorption …”

Acmella oleracea(L) R. K. Jansen Reproductive Toxicity in Zebrafish: AnIn VivoandIn SilicoAssessment

“…According to the software, M8 has a potential risk to cause cardiac insufficiency and is potentially carcinogenic for male rats and female mice. M33 is a phase I reaction (oxidation) metabolite and was predicted to be potentially carcinogenic in the liver of male mice, in the lungs of female mice, and for tumor bearer male rats [ 29 ]. The metabolite M18 was predicted to be formed through N-acetylation, one of the major routes of biotransformation from xenobiotics with an aromatic amine (R-NH 2 ), which are converted into aromatic amides (R-NH-COCH3) [ 30 ].…”

The relative risk of involvement in fatal crashes as a function of race/ethnicity and blood alcohol concentration

“…Genetically-based differences in alcohol sensitivity between Asians and Caucasians have been well documented. Differences in the prevalence of two enzymes, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), could lead to racial differences in how the alcohol is metabolized (e.g., Chan, 1986; Ramchandani, 2013). Some researchers have suggested that differences in the rates of impaired driving across racial/ethnic groups are related, among others, to differences in the way members of different racial/ethnic groups perceive the associated risk.…”