The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men.
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.
Konishi
Tamiko
T
Department of Pathology, Harbor-UCLA Research and Education Institute, Torrance, CA 90509, USA.
Calvillo
Maria
M
Leng
Ai-She
AS
Feng
Jack
J
Lee
Tony
T
Lee
Hansen
H
Smith
James Lafayette
JL
Sial
Shahid H
SH
Berman
Nancy
N
French
Samuel
S
Eysselein
Viktor
V
Lin
Keh-Ming
KM
Wan
Yu-Jui Yvonne
YJ
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
D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase