title: Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG-interferon.
abstract: In HBV-infected patients, the vitamin D deficiency has been related to chronic liver diseases, progression of hepatic fibrosis and poor response to the treatment. The CYP27B1 gene, which encodes the 1-α-hidroxylase and involved in the 1,25-dihydroxyvitamin D synthesis, was recently associated to type-1 diabetes, autoimmune disorders and treatment response in HCV. Then, we aimed to investigate the role of CYP27B1 polymorphisms in HBV treatment with PEG-IFN. We retrospectively enrolled 190 patients with chronic hepatitis B HBeAg negative treated for 48 weeks with PEG-IFN α-2a. We examined the role of rs4646536 CYP27B1 SNP (CYP27B1+2838) according to virological and serological response. Our results showed that the TT genotype of CYP27B1+2838 was significantly prevalent in patients with end-of-therapy virological response (37.6%) vs CT/CC (9.4%) (P < 0.001). Virological relapse was prevalent in patients with CT/CC genotype (12.6%) vs TT genotype (2.1%) (P < 0.001). TT genotype was also related to HBsAg loss (P = 0.004) and anti-HBs appearance (P = 0.002). In the multivariate analysis, the TT genotype resulted to be a good positive predictor of sustained virological response (OR = 5.632, IC = 1.938-16.368, P = 0.001) and serological response (OR = 6.161, IC = 1.856-20.457, P = 0.003). The CYP27B1+2838 polymorphism may be useful as pretreatment factor to selection of patients with higher probability of response to therapy.
authors: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
authors: L
authors: L
authors: Boglione
authors: J
authors: J
authors: Cusato
authors: A
authors: A
authors: De Nicolò
authors: G
authors: G
authors: Cariti
authors: G
authors: G
authors: Di Perri
authors: A
authors: A
authors: D'Avolio
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C100416:peginterferon alfa-2a
keywords: CYP27B1 polymorphism; HBV genotype; PEG-interferon therapy; hepatitis B treatment; vitamin D