[Show abstract][Hide abstract] ABSTRACT: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin.
Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers.
We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population.
Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.
Clinics (São Paulo, Brazil) 10/2013; 68(10):1325-32. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most Crohn¿s disease (CD) genes discovered in recent years are associated with biological systems critical to the development of this disease. TGFB1 and IL10 are cytokines with important roles in CD. The aim of this study was to evaluate the association between CD, its clinical features and TGFB1 and IL10 gene polymorphisms.
This case¿control study enrolled 91 patients and 91 controls from the state of Bahia, Brazil. Five single nucleotide polymorphisms (SNPs) were studied in the TGFB1 gene (codon 10 T¿>¿C - rs1800470; codon 25 G¿>¿C - rs1800471) and IL10 gene (¿1082 A¿>¿G - rs1800896; -819 T¿>¿C - rs1800871; -592 A¿>¿C - rs1800872). An analysis of the genetic polymorphisms was performed using a commercial kit. A comparison of allele frequencies and genotypes was estimated by calculating the odds ratio (OR) with a confidence interval adjusted via the Bonferroni test for a local alpha of 1%. A stratified analysis was applied for gender, race and smoking history. Patients with CD were characterized according to the Montreal classification.
The C allele and CC genotype of the TGFB1 gene rs1800470 were both significantly associated with CD. The stratified analysis showed no confounding factors for the co-variables of gender, race and smoking history. The IL10 gene rs1800896 G allele was significantly associated with age at diagnosis of CD, while the T allele of the IL10 gene rs1800871 was significantly associated with perianal disease. The SNPs rs1800871 and rs1800872 were in 100% linkage disequilibrium.
TGFB1 gene polymorphisms may be associated with susceptibility to the development of CD, and IL10 gene polymorphisms appear to influence the CD phenotype in this admixed population.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The present study aimed to evaluate the impact of animal and vegetable protein supplementation on health-related quality of life (HRQL) in patients with hepatitis C virus (HCV) and to investigate clinical and nutritional variables related to quality of life in these patients. METHODS: One hundred and forty patients infected with HCV were randomly assigned to one of two groups: the Soy Group (SG; n = 72), where patients received a soy supplement diet and the Casein Group (CG; n = 68), where patients received casein as a supplement. Anthropometric, biochemical and clinical assessments were performed in all patients, and the Short-Form Health Survey was applied at baseline and 12 weeks after study initiation. RESULTS: Before supplementation, poor HRQL scores were associated with female sex (P = 0.004) and advanced fibrosis (F3/F4; P = 0.04). Reduced HRQL scores were correlated with age (r = -0.263; P = 0.002), serum albumin levels (r = 0.245; P = 0.004), lean mass (r = 0.301; P < 0.0001) and body fat percentage (r = -0.262; P = 0.002). After 12 weeks of intervention, patients in both supplementation groups showed significantly increased HRQL scores, with no difference being observed between the SG and the CG. CONCLUSIONS: Nutritional therapy with either soybean or casein supplementation improved quality of life in patients infected with HCV. Quality of life was influenced by anthropometric, biochemical, clinical and sociodemographic factors in patients with HCV before nutritional supplementation.
Journal of Human Nutrition and Dietetics 05/2013; · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC).
In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk.
Patients' baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT.
Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients.
World Journal of Gastroenterology 05/2012; 18(18):2203-11. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 10/2011; 45(5):376-85. · 1.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not.
To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry.
rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers.
IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group.
IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.
Liver international: official journal of the International Association for the Study of the Liver 10/2011; 32(3):476-86. · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism.
This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease.
The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03).
The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease.
Clinics (São Paulo, Brazil) 01/2011; 66(8):1373-8. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Host genetic factors play an important role in mediating resistance to HIV-1 infection and may modify the course of infection. HLA-B alleles (Bw4 epitope; B*27 and B*57) as well as killer cell immunoglobulin-like receptors have been associated with slow progression of HIV-1 infection.
To evaluate the association between serological epitopes HLA-Bw4 and HLA-Bw6 and prognostic markers in AIDS.
147 HIV-infected individuals in Bahia, Northeast Brazil, were genotyped for HLA class I locus. HLA class I genotyping was performed by hybridization with sequence-specific oligonucleotide probes following amplification of the corresponding HLA-A, HLA-B and HLA-C genes. Statistical analysis was performed using Fisher's exact and ANOVA tests for categorical and continuous variables, respectively.
We detected a significant association (χ2 = 4.856; p = 0.018) between the presence of HLA-Bw4 and low levels of viremia. Eighteen out of the 147 HIV-infected individuals presented viremia <1,800 copies/mL and 129 presented viremia > 2,000 copies/mL. Ninety and four percent (17/18) of all individuals with viremia < 1,800 copies/mL carried HLA-Bw4, compared to 67.4% (87/129) of individuals with viremia > 2,000 copies/mL. Additionally, we found a significantly higher frequency of B*57 (OR = 13.94; 95% CI = 4.19-46.38; p < 0.0001) and Cw*18 (OR = 16.15; 95% CI = 3.46-75.43; p < 0.0001) alleles, favoring the group with lower viremia levels, in comparison with those with higher viral load.
HLA-Bw4-B*57 and Cw*18 alleles are associated with lower level of viral load in HIV-infected Brazilian patients. These findings may help us in understanding the determinants of HIV evolution in Brazilian patients, as well as in providing important information on immune response correlates of protection for such population.
The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 10/2010; 14(5):468-75. · 1.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy.
We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits.
We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001).
Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.
Liver international: official journal of the International Association for the Study of the Liver 04/2010; 30(4):567-73. · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection (HCV), the production of abnormal cytokine levels appears to contribute to the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes are polymorphic at specific sites, and certain polymorphisms located within coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the present study was to identify potential markers of cytokines genes associated with the susceptibility to HCV infection. The cohort was composed of 128 individuals infected by HCV and 94 healthy controls. Genotyping was carried out by PCR-SSP. The distributions of the following polymorphisms were compared in these groups: TNF-alpha (-308G/A [rs1800629]), TGF-beta1 (codon 10 T/C [rs1982073], codon 25 G/C [rs1800471]), IL-10 (-1082 A/G [rs 1800896]; -819T/C [rs1800871]; -592A/C [rs 1800872]), IL-6 (-174G/C [rs1800795]), and IFN-gamma (+874T/A [rs2430561]). This study demonstrated a statistically significant difference in the frequency of TGF-beta1 codon 25 polymorphism between healthy subjects and those infected with HCV. No associations were observed between polymorphisms of TNF-alpha, IFN-gamma, IL-10, TGF-beta1 codon 10, and IL-6 and HCV infection. These findings suggest that TGF-beta1 codon 25 polymorphism could be a host genetic factor associated with susceptibility to HCV infection.
Journal of Medical Virology 02/2008; 80(1):58-64. · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The polymorphisms in cytokine genes have allowed for the understanding of the genetic determinants of diseases. The aims of this study were to describe and compare the frequencies of polymorphisms on the interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and interferon (IFN)-gamma genes between patients with chronic pancreatitis (CP) and healthy individuals from Bahia, Brazil.
Twenty-eight individuals were evaluated at a university gastroenterology outpatient service (4 women and 24 men), all diagnosed with CP based on clinical and radiologic aspects. The control group was composed of 94 (11 women and 83 men) blood donors. The polymorphisms studied were TNF-alpha (-308G/A), TGF-beta1 (codon 10C/T, codon 25C/G), IL-10 (-1082A/G; -819T/C; -592A/C), IL-6 (-174G/C), and IFN-gamma (+874T/A).
A statistically significant difference was observed in the frequency of the polymorphisms between the group of patients with CP and the group of healthy individuals with the polymorphism of the TGF-beta1 gene on codon 10. No statistically significant differences were found for the allele and genotypic frequencies on the genes that code TNF-alpha, IFN-gamma, IL-10, and TGF-beta1 codon 25, and IL-6 between the control and case groups.
The genotypes corresponding to the high TGF-beta1 producer phenotypes can be associated with the fibrogenesis shown with CP.
[Show abstract][Hide abstract] ABSTRACT: Objectives: The polymorphisms in cytokine genes have allowed for the understanding of the genetic determinants of diseases. The aims of this study were to describe and compare the frequencies of polymorphisms on the interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and interferon (IFN)-γ genes between patients with chronic pancreatitis (CP) and healthy individuals from Bahia, Brazil.
Methods: Twenty-eight individuals were evaluated at a university gastroenterology outpatient service (4 women and 24 men), all diagnosed with CP based on clinical and radiologic aspects. The control group was composed of 94 (11 women and 83 men) blood donors. The polymorphisms studied were TNF-α (-308G/A), TGF-β1 (codon 10C/T, codon 25C/G), IL-10 (-1082A/G; -819T/C; -592A/C), IL-6 (-174G/C), and IFN-γ (+874T/A).
Results: A statistically significant difference was observed in the frequency of the polymorphisms between the group of patients with CP and the group of healthy individuals with the polymorphism of the TGF-β1 gene on codon 10. No statistically significant differences were found for the allele and genotypic frequencies on the genes that code TNF-α, IFN-γ, IL-10, and TGF-β1 codon 25, and IL-6 between the control and case groups.
Conclusion: The genotypes corresponding to the high TGF-β1 producer phenotypes can be associated with the fibrogenesis shown with CP.
[Show abstract][Hide abstract] ABSTRACT: Resumo As pancreatites se caracterizam por intenso processo inflamatório. A ativação de citocinas determina ou modula os principais mecanismos de lesão tissular local e à distância, participando dos danos que caracterizam as formas agudas ou crônicas de pancreatite. O trabalho faz uma revisão dos aspectos referentes à participação das citocinas na fisiopatologia das pancreatites, descrevendo de forma crítica as abordagens metodológicas que permitiram o seu estudo e apontando as novas modalidades de tratamento, com base na imunomodulação das citocinas. INTRODUÇÃO As citocinas são importantes reguladores da resposta imune, que modulam mecanismos fisiopatológicos que determinam a evolução de doenças. O papel das citocinas tem sido estudado em diversas condições mórbidas do trato diges-tivo, participando de processos tais como: quimiotaxia de leucócitos, determinando rea-ção inflamatória (HONG-SHAN et al., 2003); diferenciação fibroblástica e síntese de colágeno, com fibrose (VAN LAETHEM, et al., 1996); apoptose e morte celular, com necrose (YANG et al., 2003); peroxidação de lipídos, com estresse oxidativo, agressão às membranas e re-dução do metabolismo mitocondrial (DEMOLS; DEVIERE, 2003). As citocinas, portanto, interferem nos efeitos dos estímulos nóxicos, podendo mudar os quadros patológi-cos finais. As pancreatites se caracterizam por in-tenso processo inflamatório, com necrose e desencadeamento de síndrome de resposta in-flamatória sistêmica, nas formas agudas. As for-mas crônicas cursam com substituição do parênquima funcionante por tecido fibroso e catabolismo com desnutrição (SARLES et al., 1990; MEWS et al., 2002; YANG et al., 2003). Os objetivos deste trabalho são: revisar os estudos referentes à participação das citocinas na fisiopatologia das pancreatites agudas(PA) e crônicas(PC); analisar as abordagens metodo-lógicas desses estudos e apontar as novas moda-lidades terapêuticas para as pancreatites, com base na intervenção nas citocinas.
[Show abstract][Hide abstract] ABSTRACT: Cerebrospinal fluid (CSF) and serum samples from patients suspected of having neuroschistosomiasis (NS) were evaluated by an enzyme-linked immunosorbent assay. Monoclonal antibodies of various immunoglobulin isotypes (IgM, IgA, IgE, total IgG, IgG1, IgG2, IgG3, and IgG4) were used to detect antibodies against Schistosoma mansoni soluble egg antigen (SEA) and soluble worm adult preparation (SWAP). Of the 83 CSF samples tested, 55% were reactive to SEA (26% were reactive only to SEA and 29% to both SEA and SWAP), 34% were reactive to SWAP (5% only to SWAP and 29% to both SEA and SWAP), and 40% were not reactive with any antigen. Cases that tested positive for SWAP in CSF and negative in serum were not found. Samples with high specific IgG antibody titers were selected for immunoglobulin isotype profiling. In the CSF samples, the antibodies against SEA and SWAP were mainly IgM, IgG1, and IgG4, although other immunoglobulins were also detected. Interestingly, nine patients had high levels of IgG1 only in the CSF. These results suggest that there is local synthesis of IgG1, and that this isotype could be an important immunologic marker in the diagnosis of NS.
The American journal of tropical medicine and hygiene 04/2003; 68(3):294-8. · 2.74 Impact Factor