Asians, aldehyde dehydrogenase deficiency

Some populations, most notably East Asians, exhibit an unusual response after drinking ethanol. The symptoms include facial flushing, vasodilation, and tachycardia. These individuals apparently have a genetic deficiency of the enzyme aldehyde dehydrogenase, which leads to an accumulation of acetaldehyde even after they drink relatively small amounts of ethanol. If drugs such as metronidazole, griseofulvin, quinacrine, the hypoglycemic sulfonylureas, phenothiazines, and phenylbutazone are coadministered with ethanol, a similar accumulation of acetaldehyde may occur. 

Some people, primarily of Asian descent, have a genetic deficiency in the activity of the mitochondrial form of aldehyde dehydrogenase. When these individuals drink alcohol, they develop high blood acetaldehyde concentrations and experience a flushing reaction similar to that seen with the combination of disulfiram and ethanol. 

Goedde and Agarwal (96) list test results from 29 different populations and a total of 3248 subjects. The data can be summarized by the statements that Central Asian, East Asian, and South-East Asian populations showed deficiencies in the order of 30%. The deficiency was absent in European, Near-East, and African populations. North American Indians showed deficiency rates of 2-5%, South American Indians of 40-45%. O Dowd et al. (101) have shown that the functional enzyme deficiency in South American Indians must be due to a different mutation than the deficiency in Asians. This observation raises interesting questions regarding the biological significance of the mitochondrial aldehyde dehydrogenase. 

Intolerance. Inter-ethnic variation in tolerance to alcohol is well recognised, for Asian persons, particularly Japanese, develop flushing, headache and nausea after what are, by Caucasian standards, small amounts of the substance. Genetic deficiency of aldehyde dehydrogenase with slow metabolism of (toxic) acetaldehyde may explain these features. 

An interesting sidelight, Asians are often deficient in aldehyde dehydrogenase. About 50% of Japanese and Chinese people lack the mitochondrial enzyme. About 40 10 of native South Americans also lack the enzyme. This results in a number of adverse reactions to drinking alcohol, including facial flushing from dilation of peripheral blood vessels and increased heart rate. Apparently, these reactions are provoked by an unusual buildup of plasma acetaldehyde. 

Ethanol is absorbed at aU levels of the gastrointestinal tract. Acetaldehyde is the initial product of metabolism of ethanol. There are no differences between men and women in plasma levels of ethanol following its intravenous administration. Women have higher blood levels than men after oral ingestion, possibly because they have lower activity of gastric alcohol dehydrogenase. A characteristic feature of ethanol biodisposition is that its elimination via metabolism follows zero-order kinetics. Certain persons of Asian descent are deficient in aldehyde dehydrogenase and may experience a disulfiram-like reaction at low doses of ethanol. The answer is (A). 

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