RESUMO
BACKGROUND: The aim of this study was to evaluate whether polymorphisms of the mannose receptor C type 1 (MRC-1) and interleukin 28B (IL-28B) genes are associated with the treatment outcome of patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2, respectively) who are treated with peginterferon plus ribavirin (PEG-IFNα-RBV). METHODS: We analyzed the association of the patients' sustained viral responses (SVRs) to PEG-IFNα-RBV therapy with 2 single nucleotide polymorphisms (SNPs) in MRC-1 and 3 SNPs in IL-28B. We selected patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without SVR. RESULTS: Among the MRC-1 SNPs, rs691005 was found to be associated with SVR in HCV-1-infected patients (P < 0.0001). The IL-28B rs8099917 SNP was found to be associated with SVR in HCV-1- and HCV-2-infected patients (HCV-1, P < 0.0001; HCV-2, P = 0.002), while IL-28B rs955155 and rs10853728 SNPs were found to be associated with SVR in HCV-1-infected patients (P = 0.003) and HCV-2-infected patients (P = 0.02), respectively. We also identified an interaction between MRC-1 rs691005 and IL-28B rs8099917 (P = 0.001). The C-T haplotype was shown to have a positive effect on SVR in HCV-1-infected patients (OR = 1.77, 95% CI = 1.2, 2.62), whereas the T-G haplotype was shown to have a negative effect on SVR in HCV-1-infected patients (OR = 0.28, 95% CI = 0.14, 0.58). CONCLUSIONS: These results suggest that SNPs of IL-28B and MRC-1 can be used as genetic markers for predicting the outcome of PEG-IFNα-RBV treatment of HCV infections.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Receptores Imunológicos/genética , Ribavirina/uso terapêutico , Adulto , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Humanos , Interferons , Interleucinas/imunologia , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/imunologia , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND AND OBJECTIVE: Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) increased cardiomyocyte hypertrophy and apoptosis whereas Actinobaeillus actinomycetemcomitans and Prevotella intermedia had no effects. The purpose of this study is to clarify the role of calcineurin signaling pathway in P. gingivalis-induced H9c2 myocardial cell hypertrophy and apoptosis. METHODS: DNA fragmentation, nuclear condensation, cellular morphology, calcineurin protein, Bcl2-associated death promoter (Bad) and nuclear factor of activated T cell (NFAT)-3 protein products in cultured H9c2 myocardial cell were measured by agarose gel electrophoresis, DAPI, immunofluorescence, and Western blotting following P. gingivalis and/or pre-administration of CsA (calcineurin inhibitors cyclosporin A). RESULTS: P. gingivalis not only increased calcineurin protein, NFAT-3 protein products and cellular hypertrophy, but also increased DNA fragmentation, nuclear condensation and Bad protein products in H9c2 cells. The increased cellular sizes, DNA fragmentation, nuclear condensation, and Bad of H9c2 cells treated with P. gingivalis were all significantly reduced after pre-administration of CsA. CONCLUSION: Our findings suggest that the activity of calcineurin signal pathway may be initiated by P. gingivalis and further lead to cell hypertrophy and death in culture H9c2 myocardial cells.