4.7 Article

Genetic Variants in Human Leukocyte Antigen-DP Influence Both Hepatitis C Virus Persistence and Hepatitis C Virus F Protein Generation in the Chinese Han Population

Journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 15, Issue 6, Pages 9826-9843

Publisher

MDPI
DOI: 10.3390/ijms15069826

Keywords

F protein; hepatitis C virus; human leukocyte antigen-DP; polymorphism

Funding

  1. National Natural Science Foundation of China [81172724, 81202879, 30972628]
  2. Jiangsu provincial Special Program of Medical Science [BL2013021]
  3. China Mega-Project for Infectious Diseases grant from the Ministry of Science and Technology
  4. Ministry of Health [2013ZX10002005-002-005]

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Chronic hepatitis C is a serious liver disease that often results in cirrhosis or hepatocellular carcinoma. The aim of this study was to assess the association of human leukocyte antigen-DP (HLA-DP) variants with risk of chronic hepatitis C virus (HCV) or anti-F antibody generation. We selected two single nucleotide polymorphisms (SNPs) in a region including HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277534) and genotyped SNPs in 702 cases and 342 healthy controls from the Chinese population using TaqMan SNP genotyping assay. Moreover, the exon 2 of the HLA-DPA1 and HLA-DPB1 genes were amplified and determined by sequencing-based typing (SBT). The results showed that rs3077 significantly increased the risk of chronic HCV infection in additive models and dominant models (odds ratio (OR) = 1.32 and 1.53). The rs3077 also contributed to decrease the risk of anti-F antibody generation in additive models and dominant models (OR = 0.46 and 0.56). Subsequent analyses revealed the risk haplotypes (DPA1*0103-DPB1*0501 and DPA1*0103-DPB1*0201) and protective haplotypes (DPA1*0202-DPB1*0501 and DPA1*0202-DPB1*0202) to chronic HCV infection. Moreover, we also found that the haplotype of DPA1*0103-DPB1*0201 and DPA1*0202-DPB1*0202 were associated with the anti-F antibody generation. Our findings show that genetic variants in HLA-DP gene are associated with chronic HCV infection and anti-F antibody generation.

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