Alcohol dehydrogenase polymorphisms

Sachs, M.M., Dennis, E.S., Gerlach, W.L. Peacock, W.J. (1986). Two alleles of maize alcohol dehydrogenase I have 3 structural and poly(A) addition polymorphisms. Genetics, 113, 449-67. 

Developmental changes and polymorphism in human alcohol dehydrogenase. Ann Hum Genet (London) 1971 34 251-271. 

Edenberg HJ, Jerome RE, Li M. Polymorphism of the human alcohol dehydrogenase 4 (ADH4) promoter affects gene expression. Pharmacogenetics 1999 9 25-30. 

Borras E, Coutelle C, Rosell A et al. Genetic polymorphism of alcohol dehydrogenase in Europeans The ADH2 2 allele decreases the risk of alcoholism and is associated with ADH3 1. Hepatology 2000 31 984-989. 

There exists a large literature on enzyme polymorphism and species adaptation (91), but none of it can as yet be interpreted in stereochemical terms. The best-studied species is Drosophila melanogaster, in which the frequency of the two dominant alleles of alcohol dehydrogenase varies with latitude in several continents one of these alleles has a consistently lower Michaelis constant for alcohols than the other (92). The two enzymes have been found to differ by the single substitution of a lysine for... 

Other metabolic enzymes that show polymorphic differences in that they can occur as genetic high-activity and low-activity variants include acetylcholinesterase, butyrylcholinesterases, flavin-dependent monooxygenase, alcohol dehydrogenase, epoxide hydrolase, and arylesterase (Beltoft et al. 2001). 

Genetic Polymorphisms of Alcohol Dehydrogenase Modulates Alcohol Disposition and May Relate to Increased Risk of Myocardial Infarction... 

The primary pathway for alcohol metabolism involves alcohol dehydrogenase (ADH), a cytosolic enzyme that catalyzes the conversion of alcohol to acetaldehyde (Figure 23-1, left). This enzyme is located mainly in the liver, but small amounts are found in other organs such as the brain and stomach. In some Asian populations with polymorphisms in ADH that affect enzyme activity, a form of ADH with reduced activity is associated with an increased risk of alcoholism. 

Goedde HW, Agarwal DP. Aldehyde dehydrogenase polymorphism molecular basis and phenotypic relationship to alcohol sensitivity. Alcohol Alcohol 1987 (suppl l) 47-54. 

Burnell JC, Bosron WF. Genetic polymorphism of human liver alcohol dehydrogenase and kinetic properties of the isoenzymes. In Crow KE, Batt RD, eds. Human Metabolism of Alcohol. Vol. 2. Boca Raton, Florida CRC Press, Inc., 1989 65-75. 

Novoradovsky A, Tsai SJ, Goldfarb L, Peterson R, Long JC, Goldman D. Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations detection of new ALDH2 alleles. Alcohol Clin Exp Res 1999 19 1105-1110. 

TABLE 11.2. Clinically Important Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphisms... 

Matsuo K, Wakai K, Hirose K, et al. Alcohol dehydrogenase 2 His47Arg polymorphism infiuences drinking habit independently of aldehyde dehydrogenase 2 Glu487Lys polymorphism analysis of 2,299 Japanese subjects. Cancer Epidemiol Biomarkers Prev 2006 15(5) 1009-13. 

Grove J, Brown AS, Daly AK, Bassendine MF, James OF, Day CP (1998) The Rsal polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians effect on age of presentation and dependence on alcohol dehydrogenase genotype. Pharmacogenetics, 8(4) 335-342. 

E. Eliasson (2002). Oxidation of celecoxib by polymorphic cytochrome P450 2C9 and alcohol dehydrogenase. Br. J. Clin. Pharmacol 54,423-429. 

Genotype— Polymorphic forms of alcohol dehydrogenases and acetaldehyde dehydrogenases can greatly affect the rate of ethanol oxidation and the accumulation of acetaldehyde. CYP2E1 activity may vary as much as 20-fold between individuals, partly because of differences in the inducibility of different allelic variants. 

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