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Polymorphisms of HLA-DM on Treatment Response to Interferon/Ribavirin in Patients with Chronic Hepatitis C Virus Type

Hongbo Chen1, Yinan Yao2, Yifan Wang3

  • 1Department of Infectious Disease, the Jurong People's Hospital, Jurong 212400, China. chb2180@126.com.

International Journal of Environmental Research and Public Health
|October 25, 2016
PubMed

Insights

Genetic variations in HLA-DM genes, specifically rs1063478 and rs23544, significantly impact hepatitis C virus (HCV) treatment success in the Chinese Han population. Favorable genotypes increase the likelihood of sustained virological response (SVR).

Area of Science:

  • Immunogenetics
  • Hepatology
  • Pharmacogenomics

Background:

  • The Human Leukocyte Antigen (HLA)-DM gene, involved in antigen processing and presentation, is located in the non-classical class II region of the HLA complex.
  • This gene may influence treatment outcomes for chronic hepatitis C virus (HCV) infection.
  • Single nucleotide polymorphisms (SNPs) within the HLA-DM gene warrant investigation for their role in HCV treatment efficacy.

Purpose of the Study:

  • To investigate the association between specific single nucleotide polymorphisms (SNPs) in the HLA-DM gene and treatment outcomes in patients with chronic hepatitis C.
  • To evaluate the predictive value of HLA-DM gene variants for sustained virological response (SVR) following standard antiviral therapy.

Main Methods:

  • Genotyping of four SNPs within the HLA-DMA and HLA-DMB genes was performed in 336 patients undergoing treatment with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV).
  • Multivariate analysis was employed to identify independent predictors of sustained virological response (SVR).
  • Statistical analysis included logistic regression and receiver operating characteristic (ROC) curve analysis.

Main Results:

  • Two SNPs, HLA-DMA rs1063478 and HLA-DMB rs23544, were identified as independent factors influencing HCV treatment outcomes in the Chinese Han population.
  • Patients with favorable genotypes (rs1063478TT and rs23544GG) showed a significantly higher likelihood of achieving SVR (Odds Ratio [OR] ≈ 2.05).
  • Rs23544, rs1063478, baseline glucose, baseline platelet count, and T4 lymphocyte levels were independent predictors of SVR, with an Area Under the ROC Curve (AUC) of 0.740.

Conclusions:

  • Genetic variations in HLA-DM, specifically at rs1063478 and rs23544, are significantly associated with hepatitis C treatment outcomes.
  • These findings highlight the potential of HLA-DM genotype as a predictive biomarker for SVR in the Chinese Han population.
  • Further research may explore incorporating these genetic markers into personalized treatment strategies for HCV.
Abstract

Keywords:
HLA-DM genegenetic polymorphismhepatitis Ctreatment outcome

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