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Int. J. Mol. Sci. 2015, 16(2), 3213-3225; doi:10.3390/ijms16023213

Genetic Variants in the Apoptosis Gene BCL2L1 Improve Response to Interferon-Based Treatment of Hepatitis C Virus Genotype 3 Infection

1
Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark
2
Clinical Research Centre, Copenhagen University Hospital, 2650 Hvidovre, Denmark
3
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
4
Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
5
Department of Gastroenterology, Køge Hospital, 4600 Køge, Denmark
6
Department of Infectious Diseases, Hillerød Hospital, 3400 Hillerød, Denmark
7
Diagnostic Center, Silkeborg Regional Hospital, 8600 Silkeborg, Denmark
8
Department of Infectious Diseases, Odense University Hospital, 5230 Odense, Denmark
9
Department of Gastroenterology and Department of Clinical Biochemistry, Section for Molecular Diagnostics, Aalborg University Hospital, 9100 Aalborg, Denmark
10
Department of Medicine, Kolding Regional Hospital, 6000 Kolding, Denmark
11
Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark
12
Department of Hepatology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark
13
The DANHEP group (see Appendix 1)
*
Author to whom correspondence should be addressed.
Academic Editor: Ali Mobasheri
Received: 4 December 2014 / Revised: 7 January 2015 / Accepted: 26 January 2015 / Published: 2 February 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [860 KB, uploaded 2 February 2015]   |  

Abstract

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-α 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. View Full-Text
Keywords: apoptosis in HCV treatment; prediction of sustained virological response; host genetics; interferon and apoptosis interaction; spontaneous HCV resolution apoptosis in HCV treatment; prediction of sustained virological response; host genetics; interferon and apoptosis interaction; spontaneous HCV resolution
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Clausen, L.N.; Weis, N.; Ladelund, S.; Madsen, L.; Lunding, S.; Tarp, B.; Christensen, P.B.; Krarup, H.B.; Møller, A.; Gerstoft, J.; Clausen, M.R.; Benfield, T.; the DANHEP group. Genetic Variants in the Apoptosis Gene BCL2L1 Improve Response to Interferon-Based Treatment of Hepatitis C Virus Genotype 3 Infection. Int. J. Mol. Sci. 2015, 16, 3213-3225.

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