Natural killer cell receptor variants and chronic hepatitis B virus infection in the Vietnamese population

Int J Infect Dis. 2020 Jul;96:541-547. doi: 10.1016/j.ijid.2020.05.033. Epub 2020 May 16.

Abstract

Objectives: Genes of host immunity play an important role in disease pathogenesis and are determinants of clinical courses of infections, including hepatitis B virus (HBV). Killer-cell immunoglobulin-like receptor (KIR), expressed on the surface of natural killer cells (NK), regulate NK cell cytotoxicity by interacting with human leukocyte antigen (HLA) class I molecules and are candidates for influencing the course of HBV. This study evaluated whether variations in KIR gene content and HLA-C ligands are associated with HBV and with the development of liver cirrhosis and hepatocellular carcinoma.

Methods: A Vietnamese study cohort (HBV n = 511; controls n = 140) was genotyped using multiplex sequence-specific polymerase chain reaction (PCR-SSP) followed by melting curve analysis.

Results: The presence of the functional allelic group of KIR2DS4 was associated with an increased risk of chronic HBV (OR = 1.86, pcorr = 0.02), while KIR2DL2+HLA-C1 (OR = 0.62, pcorr = 0.04) and KIR2DL3+HLA-C1 (OR = 0.48, pcorr = 0.04) were associated with a decreased risk. The pair KIR2DL3+HLA-C1 was associated with liver cirrhosis (OR = 0.40, pcorr = 0.01). The presence of five or more activating KIR variants was associated with hepatocellular carcinoma (OR = 0.53, pcorr = 0.04).

Conclusions: KIR gene content variation and combinations KIR-HLA influence the outcome of HBV infection.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Human leukocyte antigen; Killer-cell immunoglobulin-like receptor; Liver cirrhosis; Natural killer cells.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / virology
  • Cohort Studies
  • Female
  • Genetic Variation
  • Genotype
  • HLA-C Antigens / genetics
  • HLA-C Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology
  • Receptors, KIR2DL2 / genetics*
  • Receptors, KIR2DL2 / immunology
  • Receptors, KIR2DL3 / genetics*
  • Receptors, KIR2DL3 / immunology
  • Vietnam
  • Young Adult

Substances

  • HLA-C Antigens
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • KIR2DS4 protein, human
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3