RESUMO
The aim of this study was to evaluate the correlation between hepatitis B virus (HBV) load and serum levels of transforming growth factor beta 1 (TGF-ß1) and soluble Fas (sFas) cytokines in human immunodeficiency virus (HIV) patients who have never been treated with antiretroviral therapy. HBV and hepatitis C virus (HCV) serological markers, sFas and TGF-ß1 levels, and HBV load were evaluated in 116 patients. While there was no correlation between TGF-ß1 levels and HBV load, a positive correlation between sFas levels and HBV load was observed in patients with occult HBV infection.
Assuntos
Coinfecção/sangue , Proteína Ligante Fas/sangue , Infecções por HIV/sangue , Vírus da Hepatite B/fisiologia , Hepatite B/sangue , Fator de Crescimento Transformador beta1/sangue , Carga Viral , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Coinfecção/virologia , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Single nucleotide polymorphisms and variant expression of some interferon (IFN) genes in individuals with chronic hepatitis B virus (HBV) infection might be related to higher viral load and disease complications. Thereby, whole blood samples of 208 patients (94 chronic HBV-infected patients and 114 HBV immune subjects) were analyzed to investigate the association between IFNG (-5Ax2192;G), IFNA1 (-2Cx2192;T) and IFNAR1 (-97Tx2192;C) genes with their expression levels and HBV viral load. METHODS: Genotyping was performed by high-resolution melting analysis with quantitative PCR (qPCR). Viral load quantification and gene expression were also carried out using qPCR. RESULTS: Chronic HBV-infected subjects with IFNA1 CT genotype and T allele were more likely to develop protection against HBV when compared to immune subjects with wild-type genotype (IFNA1 CT/CC: OR = 0.45, p = 0.01, and T/C allele: OR = 0.55; p < 0.01). In patients with IFNAR1 wild-type TT genotype, the expression levels of this receptor may explain the lower viral load (r(2) = 0.40; p = 0.04) and protection against chronic infection. CONCLUSIONS: These findings suggest that the polymorphic variant of IFNA1 (-2) gene is associated with chronic HBV infection, and high expression levels of the IFNAR1 gene and low levels of IFNA1 might contribute to the pathogenesis of chronic infection in these subjects.
Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Interferon-alfa/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor de Interferon alfa e beta/genética , Adulto , Alelos , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
Patients with acute lymphoblastic leukemia presenting the immunophenotypic marker CD10+ (calla), usually has treatment profile good. The FLT3 molecular marker is listed as a prognostic factor, an important leukaemogenic marker in acute leukemias, also the polymorphism (G1082A) of the IL10 interleukin can to present pleiotropic effects in many diseases and could is associated to development of ALL. However, the FLT3 expression is variability among patients with calla-ALL. The aim of this study was to determine the FLT3 expression, to associate with the genotypes and allelic of G1082A (IL10) in 50 patients with calla-ALL and assess the overall survival at 98 months follow-up. The expression was assessed by quantitative real time PCR (RT-PCR), the G1082A polymorphism was identified by allele-specific PCR and for immunophenotypic classification was used specific markers of B lineage-calla. We observed that patients who died showed higher FLT3 expression (p = 0.005), worse survival (p = 0.0137) and the IL10G allele may favor the survival, because the IL10 GG and IL10 GA genotypes showed a low FLT3 expression (p < 0.05).
Assuntos
Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Adolescente , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Feminino , Expressão Gênica , Estudos de Associação Genética , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Neprilisina/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
Interleukin 10 (IL10) is a pleiotropic cytokine that stimulates various hematopoietic cells. The tumor necrosis factor alpha (TNFα) is a cytokine that may influence the transcriptional activity induced by glucocorticoids. This study examined the impact of TNFα (G308A) and IL10 (G1082A) polymorphisms at promoter regions in relation to the overall survival of 105 children (0 ≤ 18 years) with acute lymphoblastic leukemia (ALL) for a period of 126 months, treated according to the protocol GBTLI99. The G1082A and G308A polymorphisms were identified by allele-specific PCR and PCR-RFLP, respectively. Patients with IL10AA genotype had a higher death ratio (44%, P = 0.0089). Patients with both IL10AA and TNFAA genotypes showed the worst survival when compared with the IL10GG and TNFGA genotypes (P = 0.0043). The results of this study revealed a lower survival among patients with IL10AA genotype and the concomitant occurrence of IL10AA and TNFAA genotypes.
RESUMO
The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001).