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Keywords:

  • BCL2L12 ;
  • cirrhosis;
  • genetics;
  • hepatitis C virus;
  • IL28B ;
  • IRF3 ;
  • polymorphism;
  • RRAS ;
  • SCAF1 ;
  • SNPs

Abstract

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.

Methods

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.

Results

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).

Conclusion

The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.