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SHR Neuro Cancer Cardio Lipid Metab Microb

Stättermayer, AF; Rutter, K; Beinhardt, S; Wrba, F; Scherzer, TM; Strasser, M; Hofer, H; Steindl-Munda, P; Trauner, M; Ferenci, P.
Role of FDFT1 polymorphism for fibrosis progression in patients with chronic hepatitis C.
Liver Int. 2014; 34(3): 388-395. Doi: 10.1111/liv.12269
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Co-authors Med Uni Graz
Trauner Michael
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Abstract:
In chronic hepatitis C (CHC), steatosis is associated with fibrosis and impaired response to antiviral therapy. Recently, a polymorphism of single nucleotide polymorphism SNP rs2645424 of farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified in NAFLD/NASH as a possible causal link to steatosis and fibrosis progression. SNP rs738409 in the adiponutrin gene (PNPLA3) is a well described factor for steatosis. This study evaluated the relation of these SNPs on steatosis, fibrosis and treatment response in CHC. The SNPs rs738409478 and rs2645424 were determined by real-time PCR in 478 patients with CHC (m/f: 314/164; mean age: 44.9 ± 10.7; GT1: 387, GT4: 91) who completed treatment with peg-IFN-α-2a/ribavirin. All had a pretreatment liver biopsy. Steatosis and fibrosis were graded by board-certified pathologists according to Brunt and METAVIR respectively. The distribution of FDFT1 rs2645424 was GG: 186 (38.9%), AG: 222 (46.4%) and AA: 70 (14.6%) and of the rs738409 PNPLA3 allele: CC: 269 (56.3%), CG: 177 (37.0%) and GG: 32 (6.7%). Overall, FDTF1 polymorphism was not linked to the extent of steatosis or fibrosis. However, in patients without steatosis the AA genotype was associated with advanced fibrosis [AA: 8/20 (40.0%), AG: 6/70 (8.5%), GG: 9/57 (16.1%), P = 0.003]. In contrast, the minor PNPLA3 allele was associated with both steatosis and advanced fibrosis (P < 0.001). Both SNPs did not influence treatment response. The minor allele in FDFT1 was associated with advanced fibrosis in the non-steatotic but not in the steatotic subgroup. This may reflect different metabolic pathways in fibrosis progression for steatotic and non-steatotic patients with CHC. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Alleles -
Antiviral Agents - therapeutic use
Disease Progression -
Farnesyl-Diphosphate Farnesyltransferase - genetics
Fatty Liver - pathology
Female -
Genotype -
Hepacivirus -
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - genetics
Humans -
Interferon-alpha - therapeutic use
Liver Cirrhosis - pathology
Logistic Models -
Male -
Middle Aged -
Polyethylene Glycols - therapeutic use
Polymorphism, Single Nucleotide -
RNA, Viral - blood
Recombinant Proteins - therapeutic use
Ribavirin - therapeutic use
Risk Factors -

Find related publications in this database (Keywords)
Chronic hepatitis C
FDFT1
fibrosis
PNPLA3
steatosis
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