The association between donor genetic variations in one-carbon metabolism pathway genes and hepatitis B recurrence after liver transplantation

Gene. 2018 Jul 15:663:121-125. doi: 10.1016/j.gene.2018.03.071. Epub 2018 Apr 5.

Abstract

Backgrounds and aim: Hepatitis B recurrence adversely affects patients' survival after liver transplantation. This study aims to find association between donor gene variations of one carbon metabolism and post-transplant hepatitis B recurrence.

Methods: This study enrolled 196 patients undergoing liver transplantation for HBV related end-stage liver diseases. We detected 11 single nucleotide polymorphisms (SNP) of 7 one-carbon metabolism pathway genes (including MTHFR, MTR, MTRR, ALDH1L1, GART, SHMT1 and CBS) in donor livers and analyzed their association with HBV reinfection after liver transplantation.

Results: Hepatitis B recurrence was observed in 19 of the 196 patients (9.7%) undergoing liver transplantation. Hepatitis B recurrence significantly affected post-transplant survival in the 196 patients (p = 0.018), and correlate with tumor recurrence in the subgroup of HCC patients (n = 99, p = 0.006). Among the 11 SNPs, donor liver mutation in rs1979277 (G > A) was adversely associated with post-transplant hepatitis B recurrence (p = 0.042). In the subgroup of HCC patients, survival analysis showed donor liver mutations in rs1801133 (G > A) and rs1979277 (G > A) were risk factors for hepatitis B recurrence (p < 0.05). None of the 11 SNPs was related to hepatitis B recurrence in non-HCC patients (n = 97, p > 0.05).

Conclusion: Hepatitis B recurrence impaired post-transplant survival. Donor liver genetic variations in one-carbon metabolism pathway genes were significantly associated with post-transplant hepatitis B recurrence.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Liver transplantation; Polymorphism.

MeSH terms

  • Adolescent
  • Adult
  • Carbon / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / virology
  • Female
  • Gene Regulatory Networks*
  • Genetic Association Studies / methods*
  • Hepatitis B / epidemiology*
  • Hepatitis B / genetics
  • Hepatitis B / mortality
  • Humans
  • Liver Diseases / genetics
  • Liver Diseases / therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / virology
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Recurrence
  • Tissue Donors
  • Young Adult

Substances

  • Carbon