Wolff (1972) demonstrated that East Asians, after drinking amounts of alcohol that have no detectable effect on Caucasians, respond with marked facial flushing and mild to moderate symptoms of intoxication. Wolff (1972) believed that group differences were attributable ... Wolff (1972) demonstrated that East Asians, after drinking amounts of alcohol that have no detectable effect on Caucasians, respond with marked facial flushing and mild to moderate symptoms of intoxication. Wolff (1972) believed that group differences were attributable to differences in autonomic reactivity. Stamatoyannopoulos et al. (1975) suggested that the racial difference in alcohol intoxication is due to rapid acetaldehyde formation as a result of the highly active atypical alcohol dehydrogenase isozyme found in high frequency in East Asians. Goedde et al. (1979) proposed that the high frequency of acute alcoholic intoxication in East Asians is related to the high frequency of persons with absence of ALDH2 liver isozyme. Individuals lacking the enzyme suffer the alcohol-flush reaction when they drink alcoholic beverages. Goedde et al. (1979) suggested that the reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption. The lower incidence of alcoholism in certain East Asian groups may have its basis in these observations. Almost all Caucasians have 2 major ALDH isozymes in the liver: cytosolic ALDH1 (100640) and mitochondrial ALDH2. Harada et al. (1980) presented evidence that aldehyde dehydrogenase is polymorphic in Japanese. As in previous studies in Europeans, they found 2 isozymes of ALDH in liver specimens of Japanese, but unlike the study of specimens of Europeans, they found that 52% of Japanese specimens showed absence of ALDH2. The authors suggested that the intoxicating symptoms after alcohol drinking in many Japanese may be due to delayed oxidation of acetaldehyde. The lack of ALDH2 is apparently responsible for the higher blood acetaldehyde levels in East Asians, leading to facial flushing and other vasomotor symptoms after alcohol intake. Agarwal et al. (1981) performed a population genetic study in Asians of several different extractions. They investigated ALDH isozymes in hair root lysates with a sensitive isoelectric focusing method. Between 40 and 80% of the several Asian groups were found to be deficient in ALDH2, whereas not a single European individual was deficient. Deficiency was invariably associated with sensitivity to alcohol. Family studies suggested autosomal recessive inheritance of the deficiency. Harada et al. (1981) found the deficiency in 43% of Japanese; all deficient persons had flushing symptoms and, after alcohol drinking, showed a mean concentration of acetaldehyde of 37.3 micromoles as compared with 2.1 micromoles in nondeficient persons. Impraim et al. (1982) found that the livers of persons lacking the ALDH2 isozyme show an enzymatically inactive but immunologically cross-reactive material (CRM) corresponding to the ALDH2 isozyme. Goedde et al. (1983) showed that the frequency of absent ALDH2 varied from 69% in Indians of the Ecuador Highlands to 44% in Japanese and 35% in Chinese to 0% in Egyptians, Liberians, Kenyans, and Europeans. They suggested that deficiency is related to flushing and a slower metabolism of acetaldehyde, and in turn a lower frequency of alcoholism and alcohol-related problems. The ALDH2 alleles encoding the active and inactive subunits are termed 'ALDH2*1' and 'ALDH2*2,' respectively; see 100650.0001. It had been thought that the 2 alleles were expressed codominantly, and that only individuals homozygous for ALDH2*2 were ALDH2-deficient. However, studies of the inheritance of alcohol-induced flushing in families suggested that the trait is dominant (Schwitters et al., 1982). Shibuya et al. (1988) studied 23 Japanese with alcoholic liver disease. No difference was found in the genotypes at the ADH2 (103720) locus; however, at the ALDH2 locus, 20 of the 23 patients were homozygous for ALDH2*1, only 3 were heterozygous, and none of the patients was homozygous for ALDH2*2. The results were interpreted as indicating that Japanese with the atypical allele are at a much lower risk for alcoholic liver disease, presumably due to their sensitivity to alcohol intoxication. In a study of 140 men and women of Chinese, Japanese, and Korean heritage, Wall et al. (2000) found that those with ALDH2*2 alleles experienced more severe hangovers and suggested that this may contribute, in part, to protection against the development of excessive or problematic drinking in Asian Americans. Yokoyama et al. (2005) found that inactive heterozygous ALDH2, alcohol flushing, and increased mean corpuscular volume (MCV) were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover. Yoshida et al. (1989) demonstrated that among Caucasians alcohol flushing can be related to abnormalities of ALDH1. In 9 unrelated Caucasian alcohol flushers, they found 1 who exhibited low activity (10-20% of normal) and another who exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these 2 samples were not altered. Immunologic quantitation indicated that the amount of protein in the 2 samples was not reduced in parallel with the enzyme deficiency. In the first case, the daughter of the proposita also had very low enzyme activity and alcohol flushing.
Among 71 Japanese nondrinkers and 268 drinkers of alcohol, Liu et al. (2005) found that drinkers had a significantly higher frequency of the 504glu (ALDH2*1) allele. Individuals with the 504lys (ALDH2*2; 100650.0001) allele had an increased risk of ... Among 71 Japanese nondrinkers and 268 drinkers of alcohol, Liu et al. (2005) found that drinkers had a significantly higher frequency of the 504glu (ALDH2*1) allele. Individuals with the 504lys (ALDH2*2; 100650.0001) allele had an increased risk of alcohol-induced flushing (odds ratio of 33.0).