title: Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women.
abstract: 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.
authors.affiliation: 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.
authors.forename: Alfons
authors.initials: A
authors.lastname: Lorenzo
authors.forename: Teresa
authors.initials: T
authors.lastname: Auguet
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
authors.forename: Montserrat
authors.initials: M
authors.lastname: Broch
authors.forename: Montserrat
authors.initials: M
authors.lastname: Olona
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Dupla
authors.forename: Joan-Josep
authors.initials: JJ
authors.lastname: Sirvent
authors.forename: Joan-Carles
authors.initials: JC
authors.lastname: Quer
authors.forename: Mauro
authors.initials: M
authors.lastname: Santos
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Richart
mesh_terms: 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*
chemical_list: 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