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. 2021 Jun 18:12:632353.
doi: 10.3389/fimmu.2021.632353. eCollection 2021.

Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population

Chao Shen  1 , Zhijun Ge  2 , Chen Dong  3 , Chunhui Wang  4   5 , Jianguo Shao  6 , Weihua Cai  7 , Peng Huang  1   5 , Haozhi Fan  8 , Jun Li  9 , Yun Zhang  4   5 , Ming Yue  9
Affiliations

Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population

Chao Shen et al. Front Immunol. .

Abstract

Background: KIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of KIR/HLA-C genes and the outcomes of HCV infection in a high-risk Chinese population.

Methods: In this case-control study, four single nucleotide polymorphisms (SNPs) of KIR/HLA-C genes (KIR2DS4/KIR2DS1/KIR2DL1 rs35440472, HLA-C rs2308557, HLA-C rs1130838, and HLA-C rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs.

Results: After logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229-1.987, P < 0.001; OR = 2.134, 95% CI: 1.180-3.858, P = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all Ptrend < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function.

Conclusion: KIR2DS4/KIR2DS1/KIR2DL1 rs35440472-A and HLA-C rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.

Keywords: hepatitis C virus; human leukocyte antigen; infection; killer cell immunoglobulin-like receptors; polymorphism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The influence of rs35440472 on KIR2DS4 mRNA optimal secondary structures. (A) The minimum free energy of the mRNA optimal secondary structure with a minimum free energy of −10.70 kcal/mol for rs35440472-A; (B) The minimum free energy of the mRNA optimal secondary structure with a minimum free energy of −11.70 kcal/mol for rs35440472-G. Changes in the local structure were illustrated by the RNAfold Web Server (Data available: http://rna.tbi.univie.ac.at//cgi-bin/RNAWebSuite/RNAfold.cgi). The arrow marks the position of the mutation (50 bases upstream and 50 bases downstream from the mutation).
See this image and copyright information in PMC

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