Association of alcohol-metabolizing genes with alcoholism in a Mexican Indian (Otomi) population.
Association studies provide a powerful approach to link DNA variants and genetic predisposition to complex diseases. In this study, we determined the genotype and allelic frequencies of genes encoding enzymes involved in alcohol metabolism in alcoholic and nonalcoholic subjects of related ethnicity. A total of 118 individuals of Otomi Mexican Indian ancestry were included. Fifty-nine were chronic alcoholics according to WHO criteria and alcohol dependents according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria. They were compared to 59 teetotalers or alcohol consumers of <10 g per day. The restriction fragment length polymorphisms analyzed were ADH1B/MaeIII, ALDH2/MboII, CYP2E1/DraI, CYP2E1/RsaI, and CYP2E1/TaqI. Of the studied polymorphisms, a significant difference between alcoholic and nonalcoholic Otomies was observed only in the CYP2E1/TaqI. The common genotype in alcoholics was A1/A2 (54%), and in nonalcoholics the homozygous A2/A2 (63%) (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.13-0.60; P=.002). The frequency of the mutant allele A1 was significantly higher in alcoholics than in nonalcoholics (41 vs. 21%; OR: 2.4; 95% CI: 1.3-4.3; P=.003). This documents the presence of a polymorphism of CYP2E1 that is overexpressed in alcoholic Otomies, in which the variant allele (A1 of CYP2E1/TaqI) is associated with increased susceptibility to alcoholism. The appreciation that this finding may be an additional factor contributing to the high frequency of liver cirrhosis in Otomies requires further investigation.
Montano Loza
Aldo J
AJ
Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Vasco de Quiroga # 15, seccion XVI, Tlalpan, CP 14000, Mexico DF. montanoa@quetzal.innsz.mx <montanoa@quetzal.innsz.mx>
Ramirez Iglesias
Maria Teresa
MT
Perez Diaz
Ivan
I
Cruz Castellanos
Socorro
S
Garcia Andrade
Consuelo
C
Medina Mora
Maria Elena
ME
Robles Díaz
Guillermo
G
Kershenobich
David
D
Gutierrez Reyes
Gabriela
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases; C027046:TCGA-specific type II deoxyribonucleases; C035594:TTTAAA -specific type II deoxyribonucleases