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.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.