Genetic Polymorphism of Alcohol Metabolyzing Enzymes and Its Implication to Human Ecology.

Abstract

Individual and racial differences in alcohol metabolism and their implications in acute and chronic intoxication of alcohol intake were reviewed in the relationships of genetic polymorphism of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The recent studies revealed that the catalytic deficiency of ALDH2 isozyme is responsible to the flushing symptom as well as other vasomotor symptoms caused by a higher acetaldehyde level after alcohol consumption. Subsequently the deficiency of ALDH2 has been prevalently found among only the peoples of Mongoloid origin and the individuals deficient in ALDH2 refrain from excessive drinking of alcohol due to averse reaction leading to protection against alcoholism. Moreover, many studies based on DNA analysis have confirmed these findings. As ALDH2 polymorphism was found only in Mongoloid, population studies on the ALDH2 mutant will provide the important information to estimate the dispersal of the ethnic groups in Asia and Oceania and also to prevent alcohol abuse in the developing countries.

Airway responsiveness to acetaldehyde in patients with asthma: relationship to methacholine responsiveness and peak expiratory flow variation

“…Ethanol is decomposed by alcohol dehydrogenase to yield acetaldehyde, which is then degraded by aldehyde dehydrogenase to yield acetic acid. Genetic polymorphism of aldehyde dehydrogenase‐2 has been well documented, and the frequency of inactive genotypes is about 50% in the Japanese but almost zero in the white European population [ 7]. It has been documented that aldehyde dehydrogenase‐2 activity is a major determining factor of asthmatic exacerbations after drinking alcoholic beverages in Japanese asthmatics [ 8, 9].…”

Quantification of skin erythema response to topical alcohol in alcohol‐intolerant East Asians

“…Extreme alcohol intolerance, characterized by flushing, headache, nausea, and tachycardia after even very modest oral alcohol consumption, affects a large fraction (more than 30%) of East Asians (Chinese, Japanese, and Koreans) . This condition is strongly associated with genetic polymorphism of aldehyde dehydrogenase (ALDH) .…”

“…Accumulation in the body of acetaldehyde causes the above symptoms of extreme alcohol sensitivity. About 30%‐40% of East Asians have a mutation of ALDH2 gene, which leads to much lower or even absence of ALDH enzyme activity. For example, after drinking 0.1 g ethanol/kg body weight, individuals who are homozygous for inactive ALDH2 and heterozygous for inactive ALDH2 had 18 times and five times higher peak blood acetaldehyde concentrations, respectively, than those who were active ALDH2*1/*1 homozygous who had consumed 0.8 g ethanol/kg body weight, and experience severe alcohol sensitivity symptoms after alcohol consumption.…”

Preparation and stability of ethanol‐free solution of [18F]florbetapir ([18F]AV‐45) for positron emission tomography amyloid imaging

“…However, because many Japanese are genetically light drinkers and we are concerned about possible side effects of ethanol, it is difficult for us to use 18 F‐labeled tracers formulated by dissolving 10% ethanol–saline solution in clinical studies. Approximately, half of the Japanese have an inherited deficiency of aldehyde dehydrogenase 2 (ALDH2) activity . People with the mutated ALDH2 allele can become very ill (disulfiram‐like reaction) after exposure to small amounts of ethanol .…”