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

Made available in DSpace on 2021-06-25T12:38:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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 30UTR), 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 HLAE*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. (C) 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. Univ Sao Paulo, Ribeirao Preto Med Sch, Div Gastroenterol, BR-14048900 Ribeirao Preto, SP, Brazil Univ Sao Paulo, Ribeirao Preto Med Sch, BR-14048900 Ribeirao Preto, SP, Brazil Univ Toronto Mississauga, Dept Anthropol, Mississauga, ON, Canada Hosp Israelita Albert Einstein, Liver Transplant Dept, BR-05652900 Sao Paulo, SP, Brazil Univ Sao Paulo, Ribeirao Preto Med Sch, Pathol Dept, BR-14048900 Ribeirao Preto, SP, Brazil Sao Paulo State Univ, Sch Med, Dept Pathol, BR-18618687 Botucatu, SP, Brazil Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14048900 Ribeirao Preto, SP, Brazil Univ Sao Paulo, Ribeirao Preto Med Sch, Immunol Div, BR-14048900 Ribeirao Preto, SP, Brazil Sao Paulo State Univ, Sch Med, Dept Pathol, BR-18618687 Botucatu, SP, Brazil CNPq: 302060/2019-7 CAPES: 001 FAPESP: 2015/26556-0