HLA-G susceptibility to hepatitis B infection and related hepatocellular carcinoma in the Japanese population

Hum Immunol. 2023 Aug;84(8):401-407. doi: 10.1016/j.humimm.2023.05.002. Epub 2023 Jun 2.

Abstract

Aims: Human leukocyte antigen (HLA)-G plays a role in various physiological immunomodulatory functions. Aberrant HLA-G expression is observed in various disease states, including tumors, autoimmune disorders, and viral infections. The present study investigated the association between HLA-G functional gene polymorphisms (rs1736933 [-486 C > A], rs1049033 [+2018 C > T], 14 bp Insertion [Ins]/Deletion [Del] [+2961 Del > Ins], and rs1063320 [+3142 C > G]) and disease susceptibility, hepatocellular carcinoma (HCC) development, and hepatitis B surface antigen (HBsAg) clearance.

Methods: Allele discrimination of the 3 SNPs (-486 C > A, +2018 C > T, +3142 C > G) was determined by a TaqMan 5' exonuclease assay, while the 14 bp Ins/Del polymorphism was typed by fragment analysis using Genetic Analyzer and GeneMapper software. The above polymorphisms were analyzed for 325 Japanese hepatitis B virus (HBV) patients, 355 Japanese healthy subjects (Controls) as healthy controls, and 799 Japanese hepatitis C virus (HCV) patients as disease controls, respectively.

Results: The 14 bp Insertion allele was significantly more frequent in HBV patients than Controls (27.1 % vs 20.6 %, odds ratio [OR] 1.43, P = 0.005) but did not differ between HCV patients and Controls. Similar results were found for the rs1063320 G allele (38.9 % vs 26.3 %, OR 1.78, P < 0.001) and the rs1736933 T allele (32.2 % vs 26.9 %, OR 1.29, P = 0.034) between HBV and Controls. The rs1049033 T allele showed a weak but significant association with HCC development in the dominant model (OR 1.95, P = 0.04). Regarding HBsAg clearance, the A allele at rs1736933 was significantly correlated in the recessive model (OR 3.23, P = 0.003).

Conclusions: This study revealed significant associations of HLA-G gene polymorphisms with disease susceptibility, HCC development, and HBsAg clearance in HBV patients.

Keywords: Hepatitis B; Human leukocyte antigen-G; Polymorphisms.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / virology
  • Case-Control Studies
  • East Asian People
  • Genetic Predisposition to Disease
  • HLA-G Antigens* / genetics
  • Hepatitis B Surface Antigens
  • Hepatitis B virus
  • Hepatitis B* / complications
  • Hepatitis B* / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / virology
  • Polymorphism, Single Nucleotide

Substances

  • Hepatitis B Surface Antigens
  • HLA-G Antigens