ABCC4, ABCC5 and SLC28A1 polymorphisms: host genome on responses of chronic hepatitis B patients with entecavir treatment

Antivir Ther. 2016;21(8):689-696. doi: 10.3851/IMP3063. Epub 2016 Jun 29.

Abstract

Background: Nucleoside drug transporter polymorphisms play a significant role in patient responses to drugs. The aim was to investigate the effect of multi-drug resistance protein 4, multi-drug resistance protein 5 and human concentrative nucleoside transporter 1 gene polymorphisms on the response to entecavir treatment in chronic hepatitis B patients.

Methods: A total of 324 chronic HBV treatment-naive Chinese Han patients treated with entecavir 0.5 mg daily for 1 year were enrolled. Patients were divided into a response group and non-response group according to the decline of HBV DNA levels. A multiplex SNaPshot single-base extension method was designed for genotyping.

Results: The rs3751333GG genotype of multi-drug resistance protein 4 was significantly different between the response group and non-response group at 6 and 12 months (P=0.005 and P=0.019, respectively). Multivariate analysis showed that the rs37751333GG genotype was significantly associated with responses at 6 and 12 months (odds ratio 2.630, 95% CI 1.391, 4.974, P=0.003; odds ratio 2.968, 95% CI 1.416, 6.221, P=0.004).

Conclusions: The multi-drug resistance protein 4 variant was significantly associated with HBV DNA level suppression in chronic hepatitis B patients treated with entecavir, and therefore, patients with the rs3751333GG genotype might respond better to entecavir in the Chinese Han population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Female
  • Genotype
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics
  • Humans
  • Male
  • Membrane Transport Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • ABCC4 protein, human
  • ABCC5 protein, human
  • Antiviral Agents
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • cif nucleoside transporter
  • entecavir
  • Guanine