Role of FDFT1 polymorphism for fibrosis progression in patients with chronic hepatitis C.
Liver Int
; 34(3): 388-95, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-23870067
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farnesil-Difosfato Farnesiltransferase
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Hepatite C Crônica
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Polimorfismo de Nucleotídeo Único
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Fígado Gorduroso
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Cirrose Hepática
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Áustria