Evaluation of the transforming growth factor beta1 codon 25 (Arg-->Pro) polymorphism in alcoholic liver disease.
BACKGROUND
Liver cirrhosis develops only in a minority of heavy drinkers. Genetic factors may account for some variation in the progression of fibrosis in alcoholic liver disease (ALD). Transforming growth factor beta 1 (TGFbeta1) is a key profibrogenic cytokine in fibrosis and its gene contains several polymorphic sites. A single nucleotide polymorphism at codon 25 has been suggested to affect fibrosis progression in patients with chronic hepatitis C virus infection, fatty liver disease, and hereditary hemochromatosis. Its contribution to the progression of ALD has not been investigated sufficiently so far.


METHODS
One-hundred-and-fifty-one heavy drinkers without apparent ALD, 149 individuals with alcoholic cirrhosis, and 220 alcoholic cirrhotics who underwent liver transplantation (LTX) were genotyped for TGFbeta1 codon 25 variants.


RESULTS
Univariate analysis suggested that genotypes Arg/Pro or Pro/Pro are associated with decompensated liver cirrhosis requiring LTX. However, after adjusting for patients' age these genotypes did not confer a significant risk for cirrhosis requiring LTX.


CONCLUSIONS
TGFbeta1 codon 25 genotypes Arg/Pro or Pro/Pro are not associated with alcoholic liver cirrhosis. Our study emphasizes the need for adequate statistical methods and accurate study design when evaluating the contribution of genetic variants to the course of chronic liver diseases.
Osterreicher
Christoph H
CH
Department of Medicine, University of California, San Diego, Leichtag Building, Room 349-I, 9500 Gilman Drive, #0702, La Jolla, CA 92093-0702, USA. coesterr@ucsd.edu
Halangk
Juliane
J
Berg
Thomas
T
Patsenker
Eleonora
E
Homann
Nils
N
Hellerbrand
Claus
C
Seitz
Helmut K
HK
Eurich
Dennis
D
Stickel
Felix
F
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D001120:Arginine / Q000235:genetics*; D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
D003062:Codon; D053773:Transforming Growth Factor beta1; D001120:Arginine; D011392:Proline