title: Association of vitamin-D-related genetic variations and treatment response to pegylated interferon in patients with chronic hepatitis B.
abstract: Vitamin D, a potent immune-modulator, has been linked to the pathogenesis of chronic hepatitis B (CHB). This study was aimed at investigating the association between single nucleotide polymorphisms (SNPs) in vitamin-D-related genes and treatment response to pegylated interferon (PEG-IFN) in patients with CHB.
  
  
  
  A total of 275 Thai patients (122 hepatitis B e antigen [HBeAg]-positive and 153 HBeAg-negative CHB) treated with 48-week PEG-IFN were recruited. Virological response (VR) at 48 weeks post-treatment was defined as HBeAg seroconversion plus HBV DNA <2,000 IU/ml for HBeAg-positive CHB and HBV DNA <2,000 IU/ml for HBeAg-negative CHB. The SNPs VDR (rs2228570), DBP (rs7041) and CYP27B1 (rs4646536) were analysed.
  
  
  
  The distribution of TT, CT and CC genotypes of rs4646536 in this cohort was 21.8%, 46.2% and 32.0%, respectively. There was no difference in its distribution according to HBeAg status. In HBeAg-positive CHB, patients with TT genotype, compared with non-TT genotype, achieved higher VR (53.3% versus 31.5%; P=0.032) and hepatitis B surface antigen (HBsAg) clearance (20.0% versus 5.4%; P=0.016). In HBeAg-negative CHB, the corresponding figures were 60.0% versus 30.9% (P=0.003) and 16.7% versus 5.7% (P=0.045), respectively. Patients with TT genotype had more rapid HBsAg decline than those with non-TT genotype. However, SNPs rs2228570 and rs7041were not associated with VR and HBsAg clearance. Logistic regression analysis demonstrated that SNP rs4646536 and baseline HBsAg level were independent predictors of VR in both HBeAg-positive and HBeAg-negative CHB.
  
  
  
  Our data suggest that SNP rs4646536 in the CYP27B1 gene is a predictive factor of response to PEG-IFN therapy in Thai patients with CHB.
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Umaporn
authors.initials: U
authors.lastname: Limothai
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Natthaya
authors.initials: N
authors.lastname: Chuaypen
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Apichaya
authors.initials: A
authors.lastname: Khlaiphuengsin
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Salyavit
authors.initials: S
authors.lastname: Chittmittraprap
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pisit
authors.initials: P
authors.lastname: Tangkijvanich
mesh_terms: D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2 / Q000008:administration & dosage / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D014807:Vitamin D
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014807:Vitamin D; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a