title: Cytotoxic T-lymphocyte antigen-4 A49G polymorphism is associated with susceptibility to and severity of alcoholic liver disease in Italian patients.
abstract: OBJECTIVE
  To determine whether the functional A49G polymorphism of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a T-cell surface molecule that modulates T-lymphocyte activation and influences the risk of developing alcohol-induced autoantibodies, plays a role in susceptibility to alcoholic liver disease (ALD) and influences disease severity in Italian alcohol abusers.
  
  
  METHODS
  One hundred and eighty-three patients with chronic ALD (61 cirrhosis), 115 end-stage HCV cirrhosis, 102 non-alcoholic fatty liver disease (NAFLD), 93 healthy subjects and 43 heavy drinkers without liver disease were studied. CTLA-4 gene polymorphism was analysed by restriction analysis.
  
  
  RESULTS
  The frequency of the CTLA-4 polymorphism was higher in patients with ALD than in patients with HCV chronic hepatitis and NAFLD, healthy subjects (P < 0.0001), and heavy drinkers without liver disease (P = 0.02). In patients with ALD, homozygosity for the CTLA-4 polymorphic allele (G/G genotype) was more represented in subjects with cirrhosis (P = 0.047), and independently associated with the risk of cirrhosis (OR 3.5; P = 0.03).
  
  
  CONCLUSIONS
  The CTLA-4 polymorphic G allele, probably by interfering with the immune response, may confer susceptibility to ALD and, in homozygous state, to alcoholic cirrhosis.
authors.affiliation: Department of Internal Medicine, University of Milan, Policlinico Hospital IRCCS, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Tullia
authors.initials: T
authors.lastname: De Feo
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.forename: Erika
authors.initials: E
authors.lastname: Fatta
authors.forename: Mario
authors.initials: M
authors.lastname: Salvagnini
authors.forename: Sarino
authors.initials: S
authors.lastname: Aricò
authors.forename: Giorgio
authors.initials: G
authors.lastname: Rossi
authors.forename: Gemino
authors.initials: G
authors.lastname: Fiorelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008108:Liver Diseases, Alcoholic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006147:Guanine; D000225:Adenine