title: A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men.
abstract: BACKGROUND
  Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD).
  
  
  METHODS
  We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model.
  
  
  RESULTS
  The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32-4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50-6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups.
  
  
  CONCLUSIONS
  To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD.
authors.affiliation: Department of Internal Medicine, University Hospital of Santiago de Compostela, A Coruña, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Novo-Veleiro
authors.affiliation: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain.|Institute of Biomedical Research of Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Cieza-Borrella
authors.affiliation: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain.|Institute of Biomedical Research of Salamanca-IBSAL, Salamanca, Spain.|Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pastor
authors.affiliation: Institute of Biomedical Research of Salamanca-IBSAL, Salamanca, Spain.|Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Antonio-Javier
authors.initials: AJ
authors.lastname: Chamorro
authors.affiliation: Institute of Biomedical Research of Salamanca-IBSAL, Salamanca, Spain.|Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Laso
authors.affiliation: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain.|Institute of Biomedical Research of Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.affiliation: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain.|Institute of Biomedical Research of Salamanca-IBSAL, Salamanca, Spain.|Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D060005:Genotyping Techniques; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics*
chemical_list: C504490:RASGRF2 protein, human; D020663:ras Guanine Nucleotide Exchange Factors