The ADH32 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men

• Published in: Experimental and molecular pathology 2003-04, Vol.74 (2), p.183-189
• Main Authors: Konishi, Tamiko, Calvillo, Maria, Leng, A.i-She, Feng, Jack, Lee, Tony, Lee, Hansen, Smith, James Lafayette, Sial, Shahid H, Berman, Nancy, French, Samuel, Eysselein, Viktor, Lin, Keh-Ming, Yvonne Wan, Y.u-Jui
• Format: Article
• Language: English
• Subjects: Adult; Alcohol dehydrogenase; Alcohol Dehydrogenase - genetics; Alcohol Drinking - adverse effects; Alcoholism; Alcoholism - genetics; Aldehyde dehydrogenase; Aldehyde Dehydrogenase - genetics; Alleles; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P450 2E1; Gene Frequency; Genotype; Humans; Male; Mexican; Mexican Americans - genetics; Middle Aged; Polymorphism, Genetic; Risk Factors; United States
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/S0014-4800(03)00006-6

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.