PLoS ONE (Jan 2017)

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.

  • Kessarin Thanapirom,
  • Sirinporn Suksawatamnuay,
  • Wattana Sukeepaisarnjareon,
  • Tawesak Tanwandee,
  • Phunchai Charatcharoenwitthaya,
  • Satawat Thongsawat,
  • Apinya Leerapun,
  • Teerha Piratvisuth,
  • Rattana Boonsirichan,
  • Chalermrat Bunchorntavakul,
  • Chaowalit Pattanasirigool,
  • Bubpha Pornthisarn,
  • Supot Tantipanichtheerakul,
  • Ekawee Sripariwuth,
  • Woramon Jeamsripong,
  • Teeranan Sanpajit,
  • Yong Poovorawan,
  • Piyawat Komolmit

DOI
https://doi.org/10.1371/journal.pone.0173263
Journal volume & issue
Vol. 12, no. 3
p. e0173263

Abstract

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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 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.