A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers
Version of Record online: 16 OCT 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 4, pages 558–566, April 2014
How to Cite
Liver Int. 2014: 34: 558–566
- Issue online: 10 MAR 2014
- Version of Record online: 16 OCT 2013
- Accepted manuscript online: 25 SEP 2013 06:57AM EST
- Manuscript Accepted: 6 SEP 2013
- Manuscript Received: 3 MAY 2013
- Red de Investigación en SIDA. Grant Numbers: ISCIII-RETIC RD06/006, ISCIII-RETIC RD12/0017
- Fundación Progreso y Salud
- Consejería de Salud de la Junta de Andalucía. Grant Number: PI-0247-2010
- Fondo de Investigaciones Sanitarias. Grant Numbers: PI10/01664, PI10/01232
- Ministerio de Sanidad y Servicios Sociales. Grant Number: EC11-304
- Fundación para la Investigación y la Prevención del Sida en España. Grant Number: 121004/10
- Instituto de Salud Carlos III. Grant Number: SCO/523/2008
- the Ministerio de Ciencia e Innovación of Sapain. Grant Number: 2001-5503-I
- Instituto de Salud Carlos III. Grant Number: Programa-I3SNS
- BCL2L12 ;
- hepatitis C virus;
- IL28B ;
- IRF3 ;
- RRAS ;
- SCAF1 ;
Background & Aims
Host genetic factors could play a primary role in determining risk for cirrhosis development in HCV-infected patients. The aims of this study were to discover new genetic variants associated with this trait and to replicate some associations formerly reported.
Three hundred and thirty-seven HCV carriers with available data about liver fibrosis status, who initiated treatment with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%) were cirrhotic. One hundred and forty-four SNPs from 40 genes related to cholesterol metabolism/transport, sustained viral response to HCV therapy, liver fibrosis, or immune response, were genotyped in all samples. Plink software was used to perform univariate association analyses. The results obtained were adjusted by other parameters related to cirrhosis using multivariate logistic regression models.
Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3 and BCL2L12 genes, was associated with cirrhosis. It was observed a higher proportion of rs12104272 A allele carriers in the non-cirrhotic group (60.63%) than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180-0.746, P = 0.006). This effect was stronger in the background of rs12979860 CC genotype of IL28B (adjusted OR = 0.069, 95% CI = 0.014–0.349, P = 0.001).
The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.