Association of CTLA4 single nucleotide polymorphisms with viral but not autoimmune liver disease.
BACKGROUND
CTLA4 is an inhibitory receptor expressed on a subset of T lymphocytes. Single nucleotide polymorphisms of the CTLA4 gene have been implicated in autoimmune diseases, including autoimmune hepatitis and primary biliary cirrhosis. In reverse form, CTLA4 variations are associated with chronic infections such as chronic hepatitis B.


METHODS
CTLA4 variations -318C>T and +49A>G were analyzed in 2366 patients with chronic liver disease of various etiologies, including 323 patients with chronic hepatitis B virus (HBV) infection, 1181 patients with chronic hepatitis C virus infection, 180 patients with primary biliary cirrhosis, and 127 patients with autoimmune hepatitis, as well as 202 healthy control individuals. Genotyping was performed by melting curve analysis.


RESULTS
The -318C>T variation was underrepresented in patients with chronic HBV infection compared with healthy controls (14.6 vs. 25.7%, P=0.002) and with patients with chronic liver disease of other origin (14.6 vs. 20.7%, P=0.011). Patients with cryptogenic cirrhosis also showed a lower frequency of the -318T allele than healthy controls (12.0 vs. 25.7%, P=0.014). No association of the +49G>A variation was found with any diagnosis, including autoimmune hepatitis and primary biliary cirrhosis.


CONCLUSIONS
We describe the association of the CTLA4 -318C>T variation with chronic HBV infection and cryptogenic cirrhosis but find no association of the +49G>A variation with autoimmune liver disease.
Department of Hepatology and Gastroenterology, Charité University Hospital Berlin, Berlin, Germany.
Eckart
E
Schott
Heiko
H
Witt
Maria
M
Pascu
Florian
F
van Boemmel
Viola
V
Weich
Alexandra
A
Bergk
Juliane
J
Halangk
Tobias
T
Müller
Gero
G
Puhl
Bertram
B
Wiedenmann
Thomas
T
Berg
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015209:Cholangitis, Sclerosing / Q000235:genetics / Q000276:immunology; D005234:Fatty Liver / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000235:genetics*; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human