Abstract
Background: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. Methods: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV). Multivariate analysis of factors predicting sustained virological response (SVR) was conducted. Results: HLA-DMA rs1063478 and DMB rs23544 were independent factors of HCV treatment outcomes in Chinese Han population. Individuals who carried favorable genotypes of rs1063478TT and rs23544GG were more likely to achieve SVR {Dominant model: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.24–3.41; OR = 2.04, 95% CI =1.23–3.35, respectively}. Rs23544, rs1063478, baseline glucose, baseline platelet and T4 level were independent predictors of SVR. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.740. Conclusions: The genetic variation of rs1063478 and rs23544 are associated with the treatment outcomes in the Chinese Han population.
Highlights
Hepatitis C virus (HCV) infection is a global public health problem affecting 160 million individuals worldwide [1]. 15%–25% of hepatitis C virus (HCV) infections can be removed in the first six months by immune response, while 75%–85% of them become chronic and develop into liver cirrhosis and hepatocellular carcinoma, and part become autoimmune disorders and lymphoma [2]
We found that patients with rs1063478 TT genotype may be prone to achieve a higher rapid virological response (RVR) rate (Recessive model: odds ratio (OR) = 2.65, 95% confidence interval (CI) = 1.16–6.06) (Supplementary Materials Table S2)
Variables are numbers of combined favorable mutants; Logistic regression analyses adjusted for age, gender, gamma-glutamyl transpeptidase, glucose, α-fetal protein, platelets, baseline RNA, T3, T4; Abbreviation: SVR, sustained virological response; N-SVR, non-sustained virological response; OR, odds ratio; CI, confidence interval; a p-value was analyzed by Cochran-Armitage trend test
Summary
Hepatitis C virus (HCV) infection is a global public health problem affecting 160 million individuals worldwide [1]. 15%–25% of HCV infections can be removed in the first six months by immune response, while 75%–85% of them become chronic and develop into liver cirrhosis and hepatocellular carcinoma, and part become autoimmune disorders and lymphoma [2]. 24 weeks after the cessation of therapy, and approximately 60%–70% sustained virological response (SVR) occurring in HCV-1 infection [4]. The human leucocyte antigen (HLA) region encodes multiple genes, which participate in antigen presentation and T cell activation [7]. Studies about hepatitis C in the United States showed that the effectiveness of antiviral treatment for blacks and whites is related to polymorphisms of MHC class-II [11]. These studies suggested that the polymorphism of MHC molecules, especially the HLA-DM and DO genes, can be regarded as genetic markers which could assist in the diagnosis, outcome prediction and prognosis. Further research on HLA-DM genes should be to be conducted to reveal the possible relationships between different HLA-DM genotypes and treatment outcomes in the Chinese Han population with chronic hepatitis C (CHC)
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