title: Genetic variants in the apoptosis gene BCL2L1 improve response to interferon-based treatment of hepatitis C virus genotype 3 infection.
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.
authors: Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark. louisenygaardclausen@gmail.com.|Clinical Research Centre, Copenhagen University Hospital, 2650 Hvidovre, Denmark. louisenygaardclausen@gmail.com.|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. louisenygaardclausen@gmail.com.
authors: Louise Nygaard
authors: LN
authors: Clausen
authors: Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark. ninaweis@dadlnet.dk.|Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. ninaweis@dadlnet.dk.
authors: Nina
authors: N
authors: Weis
authors: Clinical Research Centre, Copenhagen University Hospital, 2650 Hvidovre, Denmark. steen.ladelund.01@regionh.dk.
authors: Steen
authors: S
authors: Ladelund
authors: Department of Gastroenterology, Køge Hospital, 4600 Køge, Denmark. logm@regionsjaelland.dk.
authors: Lone
authors: L
authors: Madsen
authors: Department of Infectious Diseases, Hillerød Hospital, 3400 Hillerød, Denmark. lunding@dadlnet.dk.
authors: Suzanne
authors: S
authors: Lunding
authors: Diagnostic Center, Silkeborg Regional Hospital, 8600 Silkeborg, Denmark. brittarp@rm.dk.
authors: Britta
authors: B
authors: Tarp
authors: Department of Infectious Diseases, Odense University Hospital, 5230 Odense, Denmark. peer.christensen@dadlnet.dk.
authors: Peer Brehm
authors: PB
authors: Christensen
authors: Department of Gastroenterology and Department of Clinical Biochemistry, Section for Molecular Diagnostics, Aalborg University Hospital, 9100 Aalborg, Denmark. h.krarup@rn.dk.
authors: Henrik Bygum
authors: HB
authors: Krarup
authors: Department of Medicine, Kolding Regional Hospital, 6000 Kolding, Denmark. Axel.Moeller@slb.regionsyddanmark.dk.
authors: Axel
authors: A
authors: Møller
authors: Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark. jan.gerstoft@rh.regionh.dk.
authors: Jan
authors: J
authors: Gerstoft
authors: Department of Hepatology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark. steen.ladelund.01@regionh.dk.
authors: Mette Rye
authors: MR
authors: Clausen
authors: Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre, Denmark. steen.ladelund.01@regionh.dk.|Clinical Research Centre, Copenhagen University Hospital, 2650 Hvidovre, Denmark. steen.ladelund.01@regionh.dk.|Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. steen.ladelund.01@regionh.dk.
authors: Thomas
authors: T
authors: Benfield
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D019562:Viral Load; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D051020:bcl-X Protein; D007372:Interferons
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