Alcohol & Alcoholism Vol. 39, No. 4, pp. 276-280, 2004
Alcohol & Alcoholism Vol. 39, No. 4 © Medical Council on Alcohol 2004; all rights reserved
CYTOTOXIC T-LYMPHOCYTE ANTIGEN-4 A49G POLYMORPHISM IS ASSOCIATED WITH SUSCEPTIBILITY TO AND SEVERITY OF ALCOHOLIC LIVER DISEASE IN ITALIAN PATIENTS
1 Department of Internal Medicine, University of Milan, Policlinico Hospital IRCCS and 2 Department of Liver Transplantation, Ospedale Maggiore IRCCS, Milan, 3 Department of Gastroenterology, University of Padova, Vicenza Hospital, Venice and 4 Division of Gastroenterology, Mauriziano Hospital, Turin, Italy
* Author to whom correspondence should be addressed at: Dipartimento di Medicina Interna, Ospedale Maggiore IRCCS, Pad Granelli, Via F Sforza 35, 20122 Milano, Italy. Tel.: +39 2 5503 3757; Fax: +39 2 5032 0296; E-mail: silvia.fargion{at}unimi.it
(Received 28 October 2003; accepted 13 January 2004)
Aims: 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.
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