HLA-E gene polymorphisms in chronic hepatitis C: Impact on HLA-E liver expression and disease severity
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 polymor...
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| Veröffentlicht in: | Human immunology 2021-03, Vol.82 (3), p.177-185 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1016/j.humimm.2021.01.018 |
| format | Article |
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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.</description><identifier>ISSN: 0198-8859</identifier><identifier>EISSN: 1879-1166</identifier><identifier>DOI: 10.1016/j.humimm.2021.01.018</identifier><identifier>PMID: 33597096</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Human immunology, 2021-03, Vol.82 (3), p.177-185</ispartof><rights>2021 American Society for Histocompatibility and Immunogenetics</rights><rights>Copyright © 2021 American Society for Histocompatibility and Immunogenetics. 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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.</description><subject>Adult</subject><subject>Aged</subject><subject>Chronic hepatitis C</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis C, Chronic - genetics</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Histocompatibility Antigens Class I - metabolism</subject><subject>HLA-E Antigens</subject><subject>HLA-E gene</subject><subject>HLA-E liver expression</subject><subject>Humans</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver injury</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Young Adult</subject><issn>0198-8859</issn><issn>1879-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9LJDEQxYMo66j7DURy9NKzlf6b7EGQYVyFgb3oOaSTaidDp7s31SPOt7eHdj0KBQVVv1ePeoxdC1gKEOWv3XK7Dz6EZQqpWMKx5AlbCFmpRIiyPGULEEomUhbqnF0Q7QCggir_wc6zrFAVqHLBmsfNfbLmr9ghH_r2EPo4bD0F4r7jdhv7zlu-xcGMfvTEV7_5UxiMHXnf8Vna-jeMHN-HiER-GpvOcecJDSEnnJZ-PFyxs8a0hD8_-yV7eVg_rx6Tzd8_T6v7TWKzMh2TXIqqQSMqC6ZWmWrQWYDc5YVqMnQpOBSoTFOjkxJLVzhrXa2cqJsyzWvILtntfHeI_b890qiDJ4ttazrs96TTXAmoUiWKCc1n1MaeKGKjh-iDiQctQB8T1js9J6yPCWs4lpxkN58O-zqg-xL9j3QC7mYApz_fPEZN1mNn0fmIdtSu9987fAD_R5AQ</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Araújo, Roberta Chaves</creator><creator>Bertol, Bruna Cristina</creator><creator>César Dias, Fabricio</creator><creator>Debortoli, Guilherme</creator><creator>Almeida, Patrícia Holanda</creator><creator>Fernandes Souza, Fernanda</creator><creator>Villanova, Marcia Guimarães</creator><creator>Ramalho, Leandra Naira Zambelli</creator><creator>Candolo Martinelli, Ana Lourdes</creator><creator>Cruz Castelli, Érick da</creator><creator>Mendes Junior, Celso Teixeira</creator><creator>Antonio Donadi, Eduardo</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202103</creationdate><title>HLA-E gene polymorphisms in chronic hepatitis C: Impact on HLA-E liver expression and disease severity</title><author>Araújo, Roberta Chaves ; 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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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33597096</pmid><doi>10.1016/j.humimm.2021.01.018</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Human immunology, 2021-03, Vol.82 (3), p.177-185 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| 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 |
| title | HLA-E gene polymorphisms in chronic hepatitis C: Impact on HLA-E liver expression and disease severity |
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