title: The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men.
abstract: To identify the association between the polymorphisms of genes encoding alcohol metabolizing enzymes and alcoholism, the alcohol dehydrogenase 2 (ADH2), alcohol dehydrogenase 3 (ADH3), aldehyde dehydrogenase 2 (ALDH2), and cytochrome P450 2E1 (CYP2E1) genes were studied in 101 male Mexican American alcoholics. One hundred and four Mexican American nonalcoholic males served as controls. The allele frequency of ADH2*2 (4.3%) and ALDH2*2 (0%), which are considered as protective alleles against alcohol drinking, is very low in Mexican Americans and no association is found between these alleles and alcohol dependence. A strong association was found between ADH3 genotype and alcoholism; the percentage of subjects who carry the ADH3*2 allele was significantly higher in alcoholics (64.4%) than controls (50%). Association was also found between the CYP2E1 RsaI c2 allele and alcohol dependence; the percentage of subjects who carry the RsaI c2 allele was significantly higher in alcoholics (34.7%) than in nonalcoholics (22.1%). The subjects whose alcohol drinking onset age is younger than 25 have much higher CYP2E1 c2 allele frequency than those whose alcohol drinking onset age is older than 25 (22.1% vs 15.7%). Among 101 alcoholics, only 18 subjects carry neither ADH3*2 nor CYP2E1 c2 alleles. For those subjects who have an ADH*1/*1 background, a strong association is found between CYP2E1 RsaI/DraI genotype and alcoholism; the CYP2E1 RsaI c2 and DraI C allele frequencies are much higher in alcoholics than in nonalcoholics (26.4% vs 9.6% for c2 and 27.8% vs 13.5% for C allele). Taken together, ADH3*2 and CYP2E1 c2/C alleles might independently contribute to the development of alcoholism in Mexican American men.
authors.affiliation: Department of Pathology, Harbor-UCLA Research and Education Institute, Torrance, CA 90509, USA.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Konishi
authors.forename: Maria
authors.initials: M
authors.lastname: Calvillo
authors.forename: Ai-She
authors.initials: AS
authors.lastname: Leng
authors.forename: Jack
authors.initials: J
authors.lastname: Feng
authors.forename: Tony
authors.initials: T
authors.lastname: Lee
authors.forename: Hansen
authors.initials: H
authors.lastname: Lee
authors.forename: James Lafayette
authors.initials: JL
authors.lastname: Smith
authors.forename: Shahid H
authors.initials: SH
authors.lastname: Sial
authors.forename: Nancy
authors.initials: N
authors.lastname: Berman
authors.forename: Samuel
authors.initials: S
authors.lastname: French
authors.forename: Viktor
authors.initials: V
authors.lastname: Eysselein
authors.forename: Keh-Ming
authors.initials: KM
authors.lastname: Lin
authors.forename: Yu-Jui Yvonne
authors.initials: YJ
authors.lastname: Wan
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000483:Alleles; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014481:United States
chemical_list: D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase