Biological markers for increased risk of alcoholism and for quantitation of alcohol consumption.

Abstract

Research over the past two decades has demonstrated convincingly that there is a genetic predisposition to alcoholism (1). Alcoholism clearly shows familial clustering (2, 3), which at present has been shown to result from both inherited and environmental factors. In studies of adopted-out children of alcoholics in Sweden, two forms of alcoholism were identified. Type I alcoholism occurs in both men and women, is not usually very severe, and is associated with similar mild alcoholism which has developed in adulthood in either biological parent. It is referred to as "milieu-limited" alcoholism because both a history of alcoholism in the biological parent(s) and environmental factors are required for the development of abnormal drinking behavior in the children. A far greater risk of alcoholism was observed in the adopted-out sons of a second group of male alcoholics. These men, suffering from what was termed type II alcoholism (1-3), exhibited early onset of drinking problems (i.e., in their teens) associated with risktaking behavior, petty criminality, binge drinking, and drug abuse. The risk ofalcoholism in the sons oftype II alcoholics is about nine times the risk for males in the general population. Type II alcoholism ("male-limited" alcoholism) may account for about 25% of male alcoholics.These findings have stimulated a search for biochemical, neurophysiological, and ultimately genetic differences between alcoholics (especially type II men and their sons) and nonalcoholic control subjects. Studies on these subjects have centered on the measurement of phenotypic markers such as serum proteins, enzymes ofcirculating blood cells, and electroencephalographic studies (4). Several differences have been found between the alcoholics or sons of alcoholics and controls; these differences are described below and are in varying stages of evaluation. It is not yet known if any of the available markers are pathophysiologically related to abnormal alcoholseeking behavior or if they predict high risk for alcoholism.The acute alcohol-flushing reaction in Asians, in contrast, has been biochemically and genetically explained as the result of a single base mutation, and the reaction is clearly a protective factor against heavy drinking and alcoholism. In fact, it is the single best-characterized genetic factor influencing alcohol drinking behavior. Whether acute alcohol-flushing reactions

Differential expression of guanosine triphosphate binding proteins in men at high and low risk for the future development of alcoholism.

“…Similar to the hypothesis proposed by Nagy et al (13), we speculate that enhanced expression of Gsa sets the stage for the cell to initially undergo more pronounced activation of its AC system in the presence of alcohol, but that is then followed by more rapid and profound desensitization (e.g., tolerance). The enhanced expression of Gsa may explain the apparent phenomena of greater initial sensitivity to ethanol but more rapid development of tolerance to ethanol that develops in the offspring of alcoholics compared to nonalcoholics (6,7). For example, following an ethanol challenge, FHP men have greater sensitivity during the ascending limb of the blood ethanol curve as determined by certain autonomic measures, EMG and EEG tracings, ataxic measures, and subjective sense of intoxication (7).…”

“…In addition, sons of alcoholic fathers who are adopted before three months of age and raised in nonalcoholic households have a fourfold greater risk of developing alcoholism than sons of nonalcoholic fathers under the same circumstances (4,5). These findings have stimulated a search for biochemical, hormonal, neurophysiological, and genetic markers to identify nonalcoholic individuals at increased risk of developing alcoholism (6)(7)(8)(9)(10). There is growing evidence for differential sensitivity to the effects of ethanol secondary to differences in the metabolism of ethanol and/or differences in tissue sensitivity to ethanol (6,7,9,10).…”

Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption.

“…Future studies should address the diagnostic potential of the immunocytochemical approach in larger materials involving different stages of alcohol-associated medical disorders as well as nonalcoholic liver diseases, which are sometimes known to result in elevated endogeneous acetaldehyde levels (40). The approach would be analogous to the detection of acetaldehyde condensates with circulating proteins in order to evaluate cumulative exposure to ethanol comparable to the measurements of glucosylated hemoglobin to estimate glucose control in diabetes (17,19,41,42).…”

Genetic polymorphisms and related risk factors of ischemic stroke in a Mongolian population in China

“…ALDH2 polymorphisms play a pivotal role on hypertension (Hasi et al, 2011;Wang et al, 2013;Yokoyama et al, 2013;Hu et al, 2014), heart disease (Gu, Li, 2014;Mizuno et al, 2015) and stroke (Yao et al, 2011;Lai et al, 2012). The single base mutation (ALDH2*2) of ALDH2, the predominant allele in East Asian populations (around 70 %) (Chen, Yin, 2008), is responsible for acute alcohol-flushing reaction in Asians (Crabb, 1990). Indeed, Mongolian drinks more than other ethnic groups in China (Cochrane et al, 2003).…”