TY - JOUR
T1 - Genetic Variants in the Apoptosis Gene BCL2L1 Improve Response to Interferon-Based Treatment of Hepatitis C Virus Genotype 3 Infection
AU - Clausen, Louise Nygaard
AU - Weis, Nina
AU - Ladelund, Steen
AU - Madsen, Lone
AU - Lunding, Suzanne
AU - Tarp, Britta
AU - Christensen, Peer Brehm
AU - Krarup, Henrik Bygum
AU - Møller, Axel
AU - Gerstoft, Jan
AU - Clausen, Mette Rye
AU - Benfield, Thomas
AU - The Danhep Group
AU - Weis, Nina
AU - Barfod, Toke S
AU - Bukh, Jens
AU - Christensen, Peer Brehm
AU - Gerstoft, Jan
AU - Grønbæk, Karin
AU - Hansen, Jesper Bach
AU - Krarup, Henrik
AU - Krogsgaard, Kim
AU - Laursen, Alex Lund
AU - Lindberg, Jens
AU - Lunding, Suzanne
AU - Madsen, Lone
AU - Møller, Axel
AU - Nielsen, Henrik Ib
AU - Nielsen, Jens Ole
AU - Nørregaard, Peter
AU - Schaffalitzky de Muckadell, Ove B.
AU - Schlichting, Poul
AU - Tarp, Britta
AU - Thomsen, Reimar W.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.3390/ijms16023213
DO - 10.3390/ijms16023213
M3 - Journal article
C2 - 25648321
SN - 1661-6596
VL - 16
SP - 3213
EP - 3225
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
IS - 2
ER -