HLA-E gene polymorphisms in chronic hepatitis C: Impact on HLA-E liver expression and disease severity

• Published in: Human immunology 2021-03, Vol.82 (3), p.177-185
• Main Authors: Araújo, Roberta Chaves, Bertol, Bruna Cristina, César Dias, Fabricio, Debortoli, Guilherme, Almeida, Patrícia Holanda, Fernandes Souza, Fernanda, Villanova, Marcia Guimarães, Ramalho, Leandra Naira Zambelli, Candolo Martinelli, Ana Lourdes, Cruz Castelli, Érick da, Mendes Junior, Celso Teixeira, Antonio Donadi, Eduardo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Chronic hepatitis C; Disease Progression; Female; Gene Expression Regulation; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Hepacivirus - physiology; Hepatitis C, Chronic - genetics; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; HLA-E Antigens; HLA-E gene; HLA-E liver expression; Humans; Liver - metabolism; Liver - pathology; Liver injury; Male; Middle Aged; Polymorphism, Single Nucleotide; Young Adult
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2021.01.018

Hepatitis C virus usually produces chronic infection and liver damage. Considering that: i) the human leukocyte antigen-E (HLA-E) molecule may modulate the immune response, and ii) little is known about the role of HLA-E gene variability on chronic hepatitis C, we studied the impact of HLA-E polymorphisms on the magnitude of HLA-E liver expression and severity of hepatitis C. HLA-E variability was evaluated in terms of: i) single nucleotide polymorphism (SNP) alleles and genotypes along the gene (beginning of the promoter region, coding region and 3′UTR), and ii) ensemble of SNPs that defines the coding region alleles, considered individually or as genotypes. The comparisons of the HLA-E variation sites between patients and controls revealed no significant results. The HLA-E + 424 T > C (rs1059510), +756 G > A (rs1264457) and + 3777 G > A (rs1059655) variation sites and the HLA-E*01:01:01:01 and HLA-E*01:03:02:01 alleles, considered at single or double doses, were associated with the magnitude of HLA-E liver expression in Kupfer cell, steatosis, inflammatory activity and liver fibrosis. Although these associations were lost after corrections for multiple comparisons, these variable sites may propitiate biological clues for the understanding of the mechanisms associated with hepatitis C severity.