TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients |
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| Institution: | 1. Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;2. IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain;3. Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain;4. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;5. Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain;6. Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain;2. University of Utah Department of Pathology, 15 N Medical Drive East, Salt Lake City, UT 84112, USA;1. Department of Microbiology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong SAR, China;2. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong SAR, China;3. Research Centre of Infection and Immunology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong SAR, China;1. Institut Pasteur, Unité Biologie et Pathogénicité Fongiques – INRA USC2019, 75015 Paris, France;2. Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;3. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA;1. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan;2. Liver Research Project Center, Hiroshima University, Hiroshima, Japan;3. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan;4. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan |
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| Abstract: | BackgroundToll-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.ObjectivesTo 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 designWe 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).ResultsIn 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).ConclusionsOur 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. |
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| Keywords: | Polymorphisms HIV Chronic hepatitis C Interferon HCV therapy |
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