Genetic Variants in the Apoptosis Gene BCL2L1 Improve Response to Interferon-Based Treatment of Hepatitis C Virus Genotype 3 Infection
AbstractGenetic 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
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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.
Clausen LN, Weis N, Ladelund S, Madsen L, Lunding S, Tarp B, Christensen PB, Krarup HB, Møller A, Gerstoft J, Clausen MR, 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. International Journal of Molecular Sciences. 2015; 16(2):3213-3225.Chicago/Turabian Style
Clausen, Louise N.; Weis, Nina; Ladelund, Steen; Madsen, Lone; Lunding, Suzanne; Tarp, Britta; Christensen, Peer B.; Krarup, Henrik B.; Møller, Axel; Gerstoft, Jan; Clausen, Mette R.; Benfield, Thomas; the DANHEP group. 2015. "Genetic Variants in the Apoptosis Gene BCL2L1 Improve Response to Interferon-Based Treatment of Hepatitis C Virus Genotype 3 Infection." Int. J. Mol. Sci. 16, no. 2: 3213-3225.