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Mitochondrial ALDH2 polymorphism was initially described in Asians and is 15-17 present in 8-45% of Asian and South American Indian populations of Mongoloid origin. This dominantly inherited trait results from an inactive form of ALDH2 due to substitution of lysine for glutamate at codon 487 and it predisposes individuals to impaired metabolism of ethanol. The deficiency is absent from or occurs at very low levels among Caucasian and Negroid populations. Family studies show that phenotypically ALDH2-deficient persons possess one or two mutant alleles—i.e., are either heterozygous or homozygous—indicating the autosomal dominant inheritance of this trait. Japanese men and women who have the "Asian" type of ALDH2 drink less and suffer less from the aversive effects of alcohol than those with the active "Caucasian" ALDH2. Vasomotor dilation as revealed by "facial flushing'' is an acute reaction to ethanol that occurs in individuals homozygous and heterozygous for the ''Asian'' type of ALDH2 variant while those homozygous for the usual ALDH2 are nonflushers.

Discovery of low serum pseudocholinesterase in two Cypriot brothers that 19

resulted in prolonged apnea (paralysis of breathing) after succinylcholine ("succinylcholine sensitivity'') first suggested that the enzyme deficiency was familial and possibly hereditary. It is known to be hydrolyzed by serum cholinesterase. It is a low potency drug with very fast clearance. It produces skeletal muscle paralysis and apnea. Succinylcholine sensitivity is inherited as a relatively rare (1/2500 Caucasians) autosomal codominant trait. Persons homozygous for the mutant (atypical) form of serum cholinesterase gene have low serum cholinesterase activity and are susceptible to this disorder. At least six other low-activity hereditary variants have also been identified in association with succinylcholine sensitivity.

N-Acetyltransferase (NAT2) polymorphism was originally described for the 21, 22

metabolism of isoniazid (antituberculotic). Other drug substrates for NAT2 polymorphism affect the metabolism of aromatic amine and hydrazine drugs including hydralazine, antimicrobial sulfonamides, sulfasalazine, and procainamide as well as aromatic amine carcinogens (b-naphthylamine, 4-aminobiphenyl, and benzidine) and dietary mutagens. Individuals can be

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