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DOI: 10.1055/s-0029-1191921
Lack of an Association between CD14 Gene Variants and Disease Manifestations in Chronic Hepatitis C
Objective: Progressive hepatic fibrosis and cirrhosis develops in patients with chronic liver diseases irrespectively of etiology and with a marked inter-individual variability. Gut-derived bacterial lipopolysaccharides (endotoxin) have been shown to act as cofactors exacerbating ongoing liver disease. The T allele of a single nucleotide polymorphism (SNP), rs2569190 / C-159T, in the endotoxin receptor CD14 gene has been reported to be related to susceptibility to ethanol-induced liver cirrhosis. Our study aimed at analyzing the association of this SNP with disease progression in chronic hepatitis C. Materials and Methods: Liver biopsy specimens from a total of 137 patients with chronic hepatitis C virus (HCV) infection were evaluated regarding necroinflammatory activity (grading), architectural changes (staging), and further histological lesions characteristic for hepatitis C. HCV types, epidemiological data, and biochemical parameters were monitored in parallel. Samples of genomic DNA were genotyped at the respective position by 5rsquor;-nuclease assays using fluorescent dye-labelled allele-specific probes. Results: Genotype distribution of 30: 70: 37 (CC: CT: TT) was close to that given for Caucasians in public data bases and followed Hardy-Weinberg equilibrium (p=0.8645). Patients homozygous for the T allele were significantly younger than patients with other genotypes. However, CD14 rs2569190 / C-159T genotype was neither found to be associated with fibrosis, inflammatory activity, other histological manifestations typical for hepatitis C, HCV types, sex nor with biochemical data. Conclusion: Our data thus failed to reveal any association of CD14 rs2569190 / C-159T with clinical parameters of chronic HCV infection as it was observed by other groups (1,2).
Literatur: 1. Meiler, C., Muhlbauer, M., Johann, M., Hartmann, A., Schnabl, B., Wodarz, N., Schmitz, G., Scholmerich, J. and Hellerbrand, C. (2005) Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection. World J Gastroenterol, 11, 6031-6037. 2. Von Hahn, T., Halangk, J., Witt, H., Neumann, K., Muller, T., Puhl, G., Neuhaus, P., Nickel, R., Beuers, U., Wiedenmann, B., Berg, T. (2008) Relevance of endotoxin receptor CD14 and TLR4 gene variants in chronic liver disease. Scand J Gastroenterol, 43, 584-592.