%0 Journal Article
%T Genetic Variants in the Apoptosis Gene BCL2L1 Improve Response to Interferon-Based Treatment of Hepatitis C Virus Genotype 3 Infection
%A Louise Nygaard Clausen
%A Nina Weis
%A Steen Ladelund
%A Lone Madsen
%A Suzanne Lunding
%A Britta Tarp
%A Peer Brehm Christensen
%A Henrik Bygum Krarup
%A Axel Mller
%A Jan Gerstoft
%A Mette Rye Clausen
%A Thomas Benfield
%A the DANHEP group
%J International Journal of Molecular Sciences
%P 3213-3225
%D 2015
%I MDPI AG
%R 10.3390/ijms16023213
%X Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-¦Á and ribavirin (pegIFN/RBV) treatment of HCV genotypes 1 and 3 infections. We conducted a candidate gene association study in a prospective cohort of 201 chronic HCV-infected individuals undergoing treatment with pegIFN/RBV. Differences between groups were compared in logistic regression adjusted for age, HCV viral load and interleukin 28B genotypes. Four single nucleotide polymorphisms (SNPs) located in the B-cell lymphoma 2-like 1 ( BCL2L1) gene were significantly associated with SVR. SVR rates were significantly higher for carriers of the beneficial rs1484994 CC genotypes. In multivariate logistic regression, the rs1484994 SNP combined CC + TC genotypes were associated with a 3.4 higher odds ratio (OR) in SVR for the HCV genotype 3 ( p = 0.02). The effect estimate was similar for genotype 1, but the association did not reach statistical significance. In conclusion, anti-apoptotic SNPs in the BCL2L1 gene were predictive of SVR to pegIFN/RBV treatment in HCV genotypes 1 and 3 infected individuals. These SNPs may be used in prediction of SVR, but further studies are needed.
%K apoptosis in HCV treatment
%K prediction of sustained virological response
%K host genetics
%K interferon and apoptosis interaction
%K spontaneous HCV resolution
%U http://www.mdpi.com/1422-0067/16/2/3213