Cytotoxic T-lymphocyte antigen-4 A49G polymorphism is associated with susceptibility to and severity of alcoholic liver disease in Italian patients.
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.
Valenti
Luca
L
Department of Internal Medicine, University of Milan, Policlinico Hospital IRCCS, Italy.
De Feo
Tullia
T
Fracanzani
Anna Ludovica
AL
Fatta
Erika
E
Salvagnini
Mario
M
Aricò
Sarino
S
Rossi
Giorgio
G
Fiorelli
Gemino
G
Fargion
Silvia
S
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
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006147:Guanine; D000225:Adenine