title: Genetic variation in the vitamin D pathway CYP2R1 gene predicts sustained HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon: A multicenter study.
abstract: Evidence of a role of vitamin D in the immune system is increasing. Low serum vitamin D is associated with increased hepatitis B virus replication. Genome-wide association study (GWAS) data has revealed a number of the single nucleotide polymorphisms (SNPs) within the vitamin D synthetic pathway that affect vitamin D functions. We aimed to determine the association between SNPs in the vitamin D gene cascade and response to pegylated interferon (PegIFN) therapy in hepatitis B e-antigen (HBeAg)-positive patients. One hundred and eleven patients treated for 48 weeks with PegIFN-alfa 2a at 13 hospitals were retrospectively evaluated. Thirteen SNPs derived from vitamin D cascade-related genes, including DHCR7 (rs12785878), CYP27B1 (rs10877012), CYP2R1 (rs2060793, rs12794714), GC (rs4588, rs7041, rs222020, rs2282679), and VDR (FokI, BsmI, Tru9I, ApaI, TaqI), were genotyped. Thirty-one patients (27.9%) seroconverted to HBeAg after 24 weeks of treatment. Multivariate analysis found pretreatment qHBsAg <10,000 IU/mL (OR = 7.73, 95% CI: 2.36-25.31, P = 0.001), CYP2R1 rs12794714 TT genotype (OR = 4.16, 95% CI: 1.07-16.25, P = 0.04), and baseline ALT >2 times the upper limit of normal (OR = 3.83, 95% CI: 1.31-11.22, P = 0.014) predicted sustained HBeAg seroconversion after completion of PegIFN treatment. HBV DNA during study period tended to be lower with the rs12794714 CYP2R1 TT than the non-TT genotype. The rs12794714 CYP2R1 polymorphism may be a useful pretreatment factor predictive of sustained HBeAg seroconversion after PegIFN therapy. This study provides evidence that not only vitamin D level but also genetic variation of CYP2R1 in the vitamin D cascade influences host immune response in chronic HBV infection.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Kessarin
authors.initials: K
authors.lastname: Thanapirom
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Sirinporn
authors.initials: S
authors.lastname: Suksawatamnuay
authors.affiliation: Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Wattana
authors.initials: W
authors.lastname: Sukeepaisarnjareon
authors.affiliation: Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Bangkok, Thailand.
authors.forename: Tawesak
authors.initials: T
authors.lastname: Tanwandee
authors.affiliation: Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Bangkok, Thailand.
authors.forename: Phunchai
authors.initials: P
authors.lastname: Charatcharoenwitthaya
authors.affiliation: Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Satawat
authors.initials: S
authors.lastname: Thongsawat
authors.affiliation: Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Apinya
authors.initials: A
authors.lastname: Leerapun
authors.affiliation: Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
authors.forename: Teerha
authors.initials: T
authors.lastname: Piratvisuth
authors.affiliation: Faculty of Medicine, Vajira Hospital, Bangkok, Thailand.
authors.forename: Rattana
authors.initials: R
authors.lastname: Boonsirichan
authors.affiliation: Faculty of Medicine, Rajavithi Hospital, Bangkok, Thailand.
authors.forename: Chalermrat
authors.initials: C
authors.lastname: Bunchorntavakul
authors.affiliation: Faculty of Medicine, Police General Hospital, Bangkok, Thailand.
authors.forename: Chaowalit
authors.initials: C
authors.lastname: Pattanasirigool
authors.affiliation: Faculty of Medicine, Thammasat University Hospital, Bangkok, Thailand.
authors.forename: Bubpha
authors.initials: B
authors.lastname: Pornthisarn
authors.affiliation: Faculty of Medicine, Bhumibol Adulyadej Hospital, Bangkok, Thailand.
authors.forename: Supot
authors.initials: S
authors.lastname: Tantipanichtheerakul
authors.affiliation: Faculty of Medicine, Naresuan University, Phitsanulok, Thailand.
authors.forename: Ekawee
authors.initials: E
authors.lastname: Sripariwuth
authors.affiliation: Faculty of Medicine, Buddhachinaraj Hospital, Phitsanulok, Thailand.
authors.forename: Woramon
authors.initials: W
authors.lastname: Jeamsripong
authors.affiliation: Phramongkutklao Hospital, Bangkok, Thailand.
authors.forename: Teeranan
authors.initials: T
authors.lastname: Sanpajit
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Piyawat
authors.initials: P
authors.lastname: Komolmit
mesh_terms: D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D000072467:Cytochrome P450 Family 2 / Q000235:genetics*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C100416:peginterferon alfa-2a