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

被引:1
作者
Clausen, Louise Nygaard [1 ,2 ,3 ,4 ,5 ]
Weis, Nina [1 ,6 ]
Ladelund, Steen [2 ]
Madsen, Lone [7 ]
Lunding, Suzanne [8 ]
Tarp, Britta [9 ]
Christensen, Peer Brehm [10 ]
Krarup, Henrik Bygum [11 ,12 ]
Moller, Axel [13 ]
Gerstoft, Jan [14 ]
Clausen, Mette Rye [15 ]
Benfield, Thomas [1 ,2 ,6 ]
机构
[1] Copenhagen Univ Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark
[2] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark
[3] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, DK-2650 Hvidovre, Denmark
[4] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark
[5] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2100 Copenhagen, Denmark
[6] Univ Copenhagen, Fac Hlth Sci, Dept Clin Med, DK-2100 Copenhagen, Denmark
[7] Koge Hosp, Dept Gastroenterol, DK-4600 Koge, Denmark
[8] Hillerod Hosp, Dept Infect Dis, DK-3400 Hillerod, Denmark
[9] Silkeborg Reg Hosp, Ctr Diagnost, DK-8600 Silkeborg, Denmark
[10] Odense Univ Hosp, Dept Infect Dis, DK-5230 Odense, Denmark
[11] Aalborg Univ Hosp, Sect Mol Diagnost, Dept Gastroenterol, DK-9100 Aalborg, Denmark
[12] Aalborg Univ Hosp, Sect Mol Diagnost, Dept Clin Biochem, DK-9100 Aalborg, Denmark
[13] Kolding Reg Hosp, Dept Med, DK-6000 Kolding, Denmark
[14] Rigshosp, Copenhagen Univ Hosp, Dept Infect Dis & Rheumatol, DK-2100 Copenhagen, Denmark
[15] Rigshosp, Copenhagen Univ Hosp, Dept Hepatol, DK-2100 Copenhagen, Denmark
关键词
PLUS RIBAVIRIN; IL28B; THERAPY; ERA; POLYMORPHISM; ACTIVATION; CLEARANCE; BCL-2;
D O I
10.3390/ijms16023213
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha 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.
引用
收藏
页码:3213 / 3225
页数:13
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