TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients
Background: Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response. Objectives: To analyze the association between Toll-...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2015 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/19511 |
| Online Access: | http://hdl.handle.net/20.500.12105/19511 |
| Access Level: | Open access |
| Keyword: | Adult Alleles Antiviral Agents Coinfection Female Genotype HIV Infections Haplotypes Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Male Middle Aged Multivariate Analysis Polymorphism, Single Nucleotide Retrospective Studies Ribavirin Toll-Like Receptor 3 |
| _version_ | 1878741110751232000 |
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| author | Jimenez-Sousa, Maria Angeles |
| author2 | Rallón, Norma Berenguer, Juan Pineda-Tenor, Daniel López, Juan Carlos Soriano, Vicente Guzman-Fulgencio, Maria Cosín, Jaime Retana, Diana Garcia-Alvarez, Monica Miralles, Pilar Benito, Jose Miguel Resino, Salvador |
| author2_role | author author author author author author author author author author author author |
| author_browse | Benito, Jose Miguel Berenguer, Juan Cosín, Jaime Garcia-Alvarez, Monica Guzman-Fulgencio, Maria Jimenez-Sousa, Maria Angeles López, Juan Carlos Miralles, Pilar Pineda-Tenor, Daniel Rallón, Norma Resino, Salvador Retana, Diana Soriano, Vicente |
| author_facet | Jimenez-Sousa, Maria Angeles Rallón, Norma Berenguer, Juan Pineda-Tenor, Daniel López, Juan Carlos Soriano, Vicente Guzman-Fulgencio, Maria Cosín, Jaime Retana, Diana Garcia-Alvarez, Monica Miralles, Pilar Benito, Jose Miguel Resino, Salvador |
| author_role | author |
| collection | Repisalud |
| description | Background: Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response. Objectives: To analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients. Study design: We performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate(®) assay with VeraCode(®). The outcome variables were early virologic response (EVR) and sustained virologic response (SVR). Results: In a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039). Conclusions: Our study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_df490a5b52ee5a99a30ea337d0975b68 |
| institution | Instituto de Salud Carlos III (ISCIII) |
| instname_str | Instituto de Salud Carlos III (ISCIII) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repisalud.isciii.es:20.500.12105/19511 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | Repisalud |
| spelling | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients Jimenez-Sousa, Maria Angeles Rallón, Norma Berenguer, Juan Pineda-Tenor, Daniel López, Juan Carlos Soriano, Vicente Guzman-Fulgencio, Maria Cosín, Jaime Retana, Diana Garcia-Alvarez, Monica Miralles, Pilar Benito, Jose Miguel Resino, Salvador Adult Alleles Antiviral Agents Coinfection Female Genotype HIV Infections Haplotypes Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Male Middle Aged Multivariate Analysis Polymorphism, Single Nucleotide Retrospective Studies Ribavirin Toll-Like Receptor 3 Background: Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response. Objectives: To analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients. Study design: We performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate(®) assay with VeraCode(®). The outcome variables were early virologic response (EVR) and sustained virologic response (SVR). Results: In a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039). Conclusions: Our study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients. Elsevier http://hdl.handle.net/20.500.12105/19511 |
| spellingShingle | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients Jimenez-Sousa, Maria Angeles Adult Alleles Antiviral Agents Coinfection Female Genotype HIV Infections Haplotypes Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Male Middle Aged Multivariate Analysis Polymorphism, Single Nucleotide Retrospective Studies Ribavirin Toll-Like Receptor 3 |
| title | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
| title_full | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
| title_fullStr | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
| title_full_unstemmed | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
| title_short | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
| title_sort | TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
| topic | Adult Alleles Antiviral Agents Coinfection Female Genotype HIV Infections Haplotypes Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Male Middle Aged Multivariate Analysis Polymorphism, Single Nucleotide Retrospective Studies Ribavirin Toll-Like Receptor 3 |
| topic_facet | Adult Alleles Antiviral Agents Coinfection Female Genotype HIV Infections Haplotypes Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Male Middle Aged Multivariate Analysis Polymorphism, Single Nucleotide Retrospective Studies Ribavirin Toll-Like Receptor 3 |
| url | http://hdl.handle.net/20.500.12105/19511 |