Role of FDFT1 polymorphism for fibrosis progression in patients with chronic hepatitis C. (21st July 2013)

• Record Type: Journal Article
• Authors: Stättermayer, Albert F.; Rutter, Karoline; Beinhardt, Sandra; Wrba, Fritz; Scherzer, Thomas‐Matthias; Strasser, Michael; Hofer, Harald; Steindl‐Munda, Petra; Trauner, Michael; Ferenci, Peter
• Is Part Of: Liver international. Volume 34:Number 3(2014:Apr.)
• Page Start: 388
• Page End: 395
• Publication Date: 2013-07-21
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12269
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12269-abs-0001"> <title>Abstract</title> <sec id="liv12269-sec-0001" sec-type="section"> <title>Background</title> <p>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 (<italic>FDFT1</italic>) was identified in NAFLD/NASH as a possible causal link to steatosis and fibrosis progression. SNP rs738409 in the adiponutrin gene (<italic>PNPLA3</italic>) is a well described factor for steatosis. This study evaluated the relation of these SNPs on steatosis, fibrosis and treatment response in CHC.</p> </sec> <sec id="liv12269-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="liv12269-sec-0003" sec-type="section"> <title>Results</title> <p>The distribution of <italic>FDFT1</italic> rs2645424 was GG: 186 (38.9%), AG: 222 (46.4%) and AA: 70 (14.6%) and of the rs738409 <italic>PNPLA3</italic> allele: CC: 269 (56.3%), CG: 177 (37.0%) and GG: 32 (6.7%).</p> <p>Overall, <italic>FDTF1</italic> 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%), <italic>P</italic> = 0.003]. In contrast, the minor <italic>PNPLA3</italic> allele was associated with both steatosis and advanced fibrosis (<italic>P</italic> < 0.001).</p> <p>Both SNPs did not influence treatment response.</p> </sec> <sec id="liv12269-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The minor allele in <italic>FDFT1</italic> 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.</p> </sec> </abstract>