Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women.
BACKGROUND
The relationship of polymorphisms of the genes that encode for alcohol-metabolizing enzymes and individual vulnerability to alcoholism and alcoholic liver disease (ALD) in women is unclear. We determined the genotypes of ADH1B, ADH1C, CYP2E1 (Dra-I and Pst-I) and ALDH2 in a group of Caucasian Spanish women.


METHODS
We performed a cross-sectional case-control study. The study group was made of 220 women. Of these, 85 were alcoholic (27 without liver disease and 58 with alcoholic liver disease) and 135 were non-alcoholic (42 healthy controls and 93 with liver disease unrelated to alcohol). Genotyping of alcohol-metabolizing enzymes was performed using PCR-RFLP methods.


RESULTS
The distribution of the allelic variants (alleles 1 and 2) in the whole subjects analyzed was: ADH1B 91.6% and 8.4%; ADH1C 58.4% and 41.6%; CYP2E1 Dra-I 15% and 85%; CYP2E1 Pst-I 96.8% and 3.2%; and ALDH2 100% and 0%, respectively. Carriage of genotypes containing the ADH1B*2 mutant allele significantly protected against alcoholism [odds-ratio (OR)=0.00; 95% confidence interval (95% CI): 0.00-0.94; p=0.02] but was associated with an increased risk for alcoholic liver disease among alcohol-dependent women [OR=0.43; 95% CI: 0.18-0.41; p=0.004]. Analysis of the remaining loci showed no significant associations.


CONCLUSIONS
In Caucasian Spanish women the ADH1B*2 allele modulates the risk for alcohol dependence and for alcoholic liver disease. Given the small number of alcoholic women analyzed here, these data need further validation in larger cohorts.
Lorenzo
Alfons
A
Department of Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C/ Dr. Mallafré Guasch, 4, 43007 Tarragona, Spain.
Auguet
Teresa
T
Vidal
Francesc
F
Broch
Montserrat
M
Olona
Montserrat
M
Gutiérrez
Cristina
C
López-Dupla
Miguel
M
Sirvent
Joan-Josep
JJ
Quer
Joan-Carles
JC
Santos
Mauro
M
Richart
Cristóbal
C
D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000437:Alcoholism / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data*
D000431:Ethanol; C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial