title: Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.
abstract: Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Borràs
authors.forename: C
authors.initials: C
authors.lastname: Coutelle
authors.forename: A
authors.initials: A
authors.lastname: Rosell
authors.forename: F
authors.initials: F
authors.lastname: Fernández-Muixi
authors.forename: M
authors.initials: M
authors.lastname: Broch
authors.forename: B
authors.initials: B
authors.lastname: Crosas
authors.forename: L
authors.initials: L
authors.lastname: Hjelmqvist
authors.forename: A
authors.initials: A
authors.lastname: Lorenzo
authors.forename: C
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: M
authors.initials: M
authors.lastname: Santos
authors.forename: M
authors.initials: M
authors.lastname: Szczepanek
authors.forename: M
authors.initials: M
authors.lastname: Heilig
authors.forename: P
authors.initials: P
authors.lastname: Quattrocchi
authors.forename: J
authors.initials: J
authors.lastname: Farrés
authors.forename: F
authors.initials: F
authors.lastname: Vidal
authors.forename: C
authors.initials: C
authors.lastname: Richart
authors.forename: T
authors.initials: T
authors.lastname: Mach
authors.forename: J
authors.initials: J
authors.lastname: Bogdal
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
authors.forename: H K
authors.initials: HK
authors.lastname: Seitz
authors.forename: P
authors.initials: P
authors.lastname: Couzigou
authors.forename: X
authors.initials: X
authors.lastname: Parés
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D005060:Europe; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: D000426:Alcohol Dehydrogenase