RESUMO
INTRODUCTION AND AIMS: Celiac disease (CD) is a complex condition, whose main genetic determinant involves HLA molecules, specifically the HLA-DQ2 and/or HLA-DQ8 heterodimers. Nevertheless, the frequency of the alleles encoding those molecules has not been reported in Venezuelan celiac patients. Therefore, the aim of our study was to evaluate the frequency of the HLA-DQB1 alleles in individuals with symptoms suggestive of CD and define the diagnostic markers of the condition in a Venezuelan population. MATERIAL AND METHODS: A cross-sectional study included 516 individuals with symptoms suggestive of CD. Molecular typing of the HLA-DQB1 locus was performed using a polymerase chain reaction-sequence-specific oligonucleotide procedure (PCR-SSO). RESULTS: A total of 58.3% of the individuals with clinical manifestations consistent with CD presented with at least one risk allele (DQB1*0201 and/or DQB1*0302), and the diagnosis was confirmed in 40 of them. The patients with CD had a higher frequency of the DQB1*0201 risk allele (26.25%), followed by the DQB1*0302 (17.5%) allele. There was an association between the presence of risk alleles and the presence of lesions characteristic of CD (P = 0.001), and a correlation was found between the genetic predisposition to develop CD and the presence of anti-tissue transglutaminase antibodies (P = 0.0127). CONCLUSIONS: The results support the role of the DQB1*02 and DQB1*0302 alleles in CD susceptibility and the histologic alterations of the intestinal mucosa, in a Venezuelan population.
Assuntos
Doença Celíaca , Humanos , Alelos , Doença Celíaca/diagnóstico , Doença Celíaca/genética , Estudos Transversais , Cadeias beta de HLA-DQ/genéticaRESUMO
Current consumer preferences are determined by well-structured, full-bodied wines with a rich flavor and with reduced alcohol levels. One of the strategies for obtaining wines with reduced ethanol content is sequential inoculation of non-Saccharomyces and Saccharomyces cerevisiae yeasts. However, different factors affect the production of metabolites like ethanol, glycerol and acetic acid by inoculated yeasts. In order to obtain low alcohol wines without quality loss, the aims of our study were: i) to determine optimum conditions (fermentation temperature and time of permanence and initial inoculum size of the non-Saccharomyces population at the beginning of the process, prior to inoculation with S. cerevisiae); ii) to validate the optimized factors; and iii) to assess sensory quality of the wines obtained after validation. Two combinations of yeasts were used in this study: Hanseniaspora uvarum BHu9/S. cerevisiae BSc114 and Candida membranaefaciens BCm71/S. cerevisiae BSc114. Optimization of three fermentation factors that affect to non-Saccharomyces yeasts prior to S. cerevisiae inoculation was carried out using a Box-Behnken experimental design. Applying the models constructed by Response Surface Methodology, the lowest ethanol production by H. uvarum BHu9/S. cerevisiae BSc114 co-culture was obtained when H. uvarum BHu9 was inoculated 48â¯h 37â¯min prior to S. cerevisiae inoculation, at a fermentation temperature of 25⯰C and at an initial inoculum size of 5â¯×â¯106â¯cells/mL. Lowest alcohol production with C. membranaefaciens BCm71/S. cerevisiae BSc114 was observed when C. membranaefaciens BCm71 was inoculated 24â¯h 15â¯min prior to S. cerevisiae at a fermentation temperature of 24.94⯰C and at an initial inoculum size of 2.72â¯×â¯106â¯cells/mL. The optimized conditions of the two co-cultures were subsequently submitted to lab-scale validation. Both proposed strategies yielded ethanol levels that were significantly lower than control cultures (S. cerevisiae). Wines fermented with non-Saccharomyces/Saccharomyces co-cultures under optimized conditions were also associated with higher aromatic complexity characterized by the presence of red fruit aromas, whereas wines obtained with S. cerevisiae BSc114 were described by parameters linked with high ethanol levels.
Assuntos
Etanol/metabolismo , Fermentação , Microbiologia de Alimentos/métodos , Vinho/microbiologia , Leveduras/metabolismo , Ácido Acético/metabolismo , Reatores Biológicos , Técnicas de Cocultura , Odorantes , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Vinho/normas , Leveduras/crescimento & desenvolvimentoRESUMO
BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and ß, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS). RESULTS: One hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R ß was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01). CONCLUSIONS: IGF-1R ß overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/radioterapia , Tolerância a Radiação/fisiologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radioterapia/métodos , Neoplasias do Colo do Útero/mortalidadeRESUMO
Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N-Si bond. The reaction is initiated by Nâ activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N-Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosomaâ brucei and T.â cruzi, featuring favorable drug-like properties and safety profiles.
Assuntos
Antiparasitários/farmacologia , Cianetos/química , Hidrazinas/química , Nitrogênio/química , Silício/química , Trypanosoma cruzi/efeitos dos fármacos , Antiparasitários/síntese química , Antiparasitários/química , Estrutura Molecular , Testes de Sensibilidade ParasitáriaRESUMO
INTRODUCTION: Several studies have reported increased oxidation of lipids, proteins and DNA in the brains of patients with Alzheimer disease (AD). Moreover, these patients display differences in the activity and polymorphisms of the genes encoding the enzymes GST (T1, M1) and MnSOD. For these reasons, we designed a study of the variability in GSTT1, GSTM1, and MnSOD genes in healthy and AD groups from a Venezuelan population. METHODS: We included 179 unrelated Venezuelan subjects classified as either AD patients (n=79) or healthy individuals (n=100). Presence or absence of the GSTT1/GSTM1 genes was determined using PCR-SSP, and polymorphisms of MnSOD and APOE genes were identified with PCR-RFLP. RESULTS: The genotype GSTT1+/GSTM1- seems to favour development of AD (OR=2.06, P=.01). The risk level is higher when it is combined with the É4 allele of the APOE gene: GSTT1+/GSTM1-/É3É4 (OR=3.07, P=.05), GSTT1+/GSTM1-/É4É4 (OR=5.52, P=.02). The Ala-9Val polymorphism does not appear to be related to AD. However, the presence of the Ala/Ala genotype increases the risk provided by the É4 allele of the APOE gene: AlaAla/É3É4 (OR=3.47, P=.03), AlaAla/É4É4 (OR=6.3, P=.01). CONCLUSIONS: The results support the hypothesis that impaired mitochondrial function and increased oxidative damage are involved in the pathogenesis of AD. It is important to study other genes related to oxidative stress and antioxidant pathways which could be involved in susceptibility to AD.
Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Glutationa Transferase/genética , Superóxido Dismutase/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Polimorfismo Genético/genética , Venezuela/epidemiologiaRESUMO
Prefermentative cold soak is a widely used technique in red wine production, but the impact on the development of native yeast species is hardly described. The aim of this work was to analyse the dynamics and diversity of yeast populations during prefermentative cold soak in red wines. Three different temperatures (14 ± 1 °C; 8 ± 1 °C and 2.5 ± 1 °C) were used for prefermentative cold soak in Cabernet Sauvignon and Malbec grape musts. Saccharomyces and non-Saccharomyces populations during cold soak and alcoholic fermentation were analysed. In addition, the impact on chemical and sensory properties of the wines was examined. Yeast dynamics during prefermentative cold soak were temperature dependent. At 14 ± 1 °C, the total yeast population progressively increased throughout the cold soak period. Conversely, at 2.5 ± 1 °C, the yeast populations maintained stable during the same period. Prefermentative cold soak conducted at 14±1°C favoured development of Hanseniospora uvarum and Candida zemplinina, whereas cold soak conducted at 8 ± 1 °C favoured growth of Saccharomyces cerevisiae. At 2.5 ± 1 °C, no changes in yeast species were recorded. Acidity and bitterness, two sensory descriptors, appear to be related to wines produced with prefermentative cold soak carried out at 14 ± 1 °C. This fact could be associated with the increase in non-Saccharomyces during the prefermentation stage. Our results emphasise the importance of the temperature as a determinant factor to allow an increase in non-Saccharomyces population during prefermentative cold soak and consequently to modify sensorial attributes of wines as well as their sensorial impact.
Assuntos
Temperatura Baixa , Vitis/microbiologia , Água , Vinho/microbiologia , Leveduras/fisiologia , Fermentação , Dinâmica Populacional , Saccharomyces/crescimento & desenvolvimento , Saccharomyces/fisiologia , Paladar , Vinho/análise , Leveduras/crescimento & desenvolvimento , Leveduras/metabolismoRESUMO
Bacterial protein toxins are important virulence factors. A particular class of toxins, the pore-form toxins (PFTs), shares the toxigenic mechanism of forming pores in the membrane of target cells. The relationship between autophagy and bacterial PFTs has been described for several toxin-secreting pathogens and in this review we have recapitulated the more recent findings on this issue. A common outcome is that the target cell, by a yet non-completely defined mechanism, senses the toxin attack and builds up complex responses as a protective mechanism for host survival. However, in some cases, this cellular response is beneficial to the microorganism by supplying an intracellular niche or by promoting host-cell death, which facilitates pathogen spreading.
Assuntos
Autofagia/genética , Toxinas Bacterianas/toxicidade , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Proteínas Citotóxicas Formadoras de Poros/toxicidade , Fatores de Virulência/toxicidade , Toxinas Bacterianas/metabolismo , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sobrevivência Celular/genética , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/patogenicidade , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Fagossomos/efeitos dos fármacos , Fagossomos/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Virulência/metabolismoRESUMO
Nothofagus nervosa (Raulí) is a native tree species that yields valuable timber. It was overexploited in the past and is currently included in domestication and conservation programs. Several research programs have focused on the characterization of epiphytic microorganisms because it has been demonstrated that they can affect plant-pathogen interactions and/or promote plant growth. Although the microbial ecology of leaves has been well studied, less is known about microorganisms occurring on seeds and noncommercial fruits. In this work, we analyzed the yeast and yeast-like fungi present on N. nervosa fruits destined for the propagation of this species, as well as the effects of fruit preservation and seed dormancy-breaking processes on fungal diversity. Morphological and molecular methods were used, and differences between fungal communities were analyzed using a similarity index. A total of 171 isolates corresponding to 17 species were recovered, most of which belong to the phylum Ascomycota. The majority of the species develop mycelia, produce pigments and mycosporines, and these adaptation strategies are discussed. It was observed that the preservation process considerably reduced yeast and yeast-like fungal diversity. This is the first study concerning microbial communities associated with this ecologically and economically important species, and the information presented is relevant to domestication programs.
Assuntos
Fungos/classificação , Magnoliopsida/microbiologia , Leveduras/classificação , Argentina , Sequência de Bases , Frutas/microbiologia , Fungos/genética , Fungos/crescimento & desenvolvimento , Fungos/isolamento & purificação , Dados de Sequência Molecular , Sementes/microbiologia , Leveduras/genética , Leveduras/crescimento & desenvolvimento , Leveduras/isolamento & purificaçãoRESUMO
Soil microorganisms play an important role in soil quality and they interact closely with vegetation. Little is known about yeast diversity and function in forest soil ecosystems and their interactions with other biotic soil components, particularly in the mycorrhizosphere. We studied the diversity of yeasts inhabiting the bulk-soil, rhizosphere and ectomycorrhizosphere of a Nothofagus pumilio forest in Nahuel Huapi National Park (Bariloche, Argentina). Ectomycorrhizal infection was observed in all N. pumilio trees studied. A total of 126 yeast isolates were obtained, including 18 known and three possibly new species. Basidiomycetous yeasts were predominant in all soil fractions, and the most frequently isolated species was Cryptococcus podzolicus. Diversity indices and multivariate analyses were used to study and compare yeast communities in the bulk-soil, rhizosphere and ectomycorrhizosphere. Yeasts able to ferment glucose were found associated with the rhizosphere. Many of the recovered yeast species were associated with lignocelluloses compound degradation, which suggest that yeast plays an important role as a decomposer in these forest soils. Each soil fraction has a distinct yeast assemblage related to their physiologic capacities and soil nutrient availability.
Assuntos
Biodiversidade , Rizosfera , Microbiologia do Solo , Árvores/microbiologia , Leveduras/isolamento & purificação , Argentina , Análise por Conglomerados , Contagem de Colônia Microbiana , DNA Fúngico/genética , Glucose/metabolismo , Lignina/metabolismo , Magnoliopsida/microbiologia , Micorrizas/genética , Micorrizas/crescimento & desenvolvimento , Micorrizas/isolamento & purificação , Micorrizas/metabolismo , Análise de Sequência de DNA , Solo/análise , Leveduras/genética , Leveduras/crescimento & desenvolvimento , Leveduras/metabolismoRESUMO
Two strains of a novel yeast species were isolated from ectomycorrhizal Nothofagus pumilio rhizospheric soil in a native forest of Patagonia, Argentina. Analysis of the D1/D2 large-subunit rRNA gene sequences indicated that the novel species belongs to the recently described genus Lindnera. The name Lindnera rhizosphaerae sp. nov. is proposed to accommodate these isolates, and the type strain is CRUB 1796(T) (â=âCBS 11400(T) â=âJCM 16499(T)).
Assuntos
Gleiquênias/microbiologia , Rizosfera , Saccharomycetales/classificação , Saccharomycetales/isolamento & purificação , Microbiologia do Solo , Argentina , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Genes de RNAr , Dados de Sequência Molecular , Filogenia , RNA Fúngico/genética , RNA Ribossômico/genética , Saccharomycetales/genética , Análise de Sequência de DNARESUMO
This study represents the first report on the distribution of KIR genes in 205 unrelated healthy mestizo Venezuelan individuals. Genotyping analysis showed that all KIR genes are present in this population. Frequency of inhibitory killer cell immunoglobulin-like receptors (KIRs) exceeded 0.69, except for KIR2DL2 (0.29) and 2DL5 (0.37). Activating KIRs showed low frequencies (0.11-0.29), except for KIR2DS4 (0.68). Forty-five different KIR genotypes were identified, with a predominance of three genotypes found in 50.7% of the population of which 25.9% were individuals homozygous for haplotype A. The frequencies of KIR genes reflect the ethnic admixture existing in the mestizo Venezuelan population.
Assuntos
Frequência do Gene , População/genética , Receptores KIR/genética , Humanos , Filogenia , VenezuelaRESUMO
Six strains of a novel yeast species were isolated from Nothofagus species trees in native forests in Patagonia, Argentina. The strains were isolated from bark, fluxes and the ectomycorrhizospheric soil fraction of Nothofagus antarctica, Nothofagus nervosa and Nothofagus pumilio. Analysis of the D1/D2 large-subunit rDNA sequences indicated that the novel species belonged to the genus Lachancea and is closely related to Lachancea meyersii. The name Lachancea nothofagi sp. nov. is proposed to accommodate these strains. The type strain is UWOPS 99-807.3(T) (=CBS 11611(T)=NRRL Y-48670(T)).
Assuntos
Magnoliopsida/microbiologia , Saccharomycetales/classificação , Saccharomycetales/isolamento & purificação , Microbiologia do Solo , DNA Fúngico/genética , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , Saccharomycetales/genéticaRESUMO
La Enfermedad celíaca es una enteropatía caracterizada por malabsorción y daño epitelial del intestino delgado, del cual se han aislado células T específicas al gluten y restringidas a los heterodímeros DQ2-DQ8, sugiriendo que los alelos DQ juegan un papel clave en la patogénesis de la enfermedad por la presentación de péptidos derivados del gluten a linfocitos T de la mucosa. En nuestro estudio evaluamos el polimorfismo HLA-DQA y DQB en pacientes pediátricos con Enfermedad Celiaca. Se estudiaron 16 pacientes que acudieron al Servicio de Gastroenterología Pediátrica del Hospital "JM de los Ríos". Los polimorfismos se definieron mediante PCR-secuenciación; las asignaciones alélicas y haplotípicas se determinaron por contaje directo. En concordancia con estudios realizados en otras poblaciones, este estudio sugiere que los heterodímeros HLA-DQ2 y DQ8 son marcadores genéticos de predisposición al desarrollo de la enfermedad celíaca. Siendo este reporte el primero en el País en resaltar la presencia de los HLA en la enfermedad celíaca.
The celiac disease is an enteropathy characterized by malabsortion and epitelial damage of the small bowel, of the one which cells specific T has been isolated to gluten and restricted to the DQ2-DQ8 heterodímers, suggesting that the DQ alelles play a key role in the pathogenesis of the disease for the presentation of derived péptides from the gluten to T linfocites. In our study we evaluate the HLA-DQA and DQB polymorphism in pediatric patients with celiac Disease. 16 patients were studied from Gastroenterology service of the "Hospital de Niños JM de los Ríos". The polymorphism was defined through PCR-sequence; the assignments of alleles and haplotype were determined by direct count. Similar to other reports which suggest HLA DQ2 y DQ8 as markers in genetic predisposition in celiac disease, this study is the first in Venezuela in screened HLA in Celiac Disease.
RESUMO
The two basic forms of autoimmune intraepidermal blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), affect different layers of the skin, have different symptoms and target different antigens. We have defined human leukocyte antigen (HLA)-DRB1-DQB1 alleles and haplotypes in a case-control study of 66 non-Jewish patients attending a public reference Hospital over the past 10 years. The control group consisted of 101 matched individuals tested also by medium to high-resolution polymerase chain reaction-sequence-specific oligonucleotide with primers and probes from the 12th and 13th International Histocompatibility Workshop. Patients and controls were descendants of three-generation individuals born in the country. Among the patients, 49 had PV, 50% showed predominantly mucosal involvement, 50% showed predominantly the cutaneous clinical phenotype and 17 had PF. Statistically significant HLA-DR frequency differences between patients with PV and controls were found only for DRB1*0402 and DRB1*1401 [odds ratio (OR) = 27.22, confidence interval (CI) 94.7-7.82, P= 1.1 x 10(-14) and OR = 46.56, CI 801.4-2.70 P= 7.5 x 10(-6), respectively]. Both alleles were also increased in the patients with PF compared with the controls (OR = 7.0, P= 0.038 and OR = 21.64, P= 0.009, respectively), but the significance of the difference did not resist Bonferroni correction. Haplotype analysis showed that DRB1*0402 was always present with DQB1*0302 and DRB1*1401 with DQB1*0503, but no independent effect of the DQB1*0302 in the former haplotype was evident. Our results support the hypothesis that the DRB1*0402 without DQB1*0302 is the most relevant HLA-DRB1 allele responsible for the pathogenesis of pemphigus in Venezuelan patients with PV and discard the DQB1*0302 influence observed in other populations.
Assuntos
Predisposição Genética para Doença , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Pênfigo/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Pênfigo/etnologia , Estudos Prospectivos , VenezuelaRESUMO
Previous studies carried out in an endemic semiarid region northwest of Venezuela at Falcon State have shown a prevalence of 15.4/1000 of chromoblastomycosis following traumatisms with xenophile vegetation infected with Cladophialophora carrionii. We performed high-resolution DNA typing of human leukocyte antigen (HLA)-A, -B and -C and major histocompatibility complex class I chain related gene A (MICA) alleles and segregation analysis in 49 members of one extended family with 12 affected individuals, who have lived for approximately 70 years in this endemic zone. None of the alleles, haplotypes or genotypes is shared by all the patients. No deviation from the expected HLA haplotype distribution or association of chromoblastomycosis with HLA-A, -B and -C haplotypes was observed. Further, a haplotype-sharing transmission/disequilibria testing of 11 nuclear families did not give enough evidence to claim linkage (P = 0.398), suggesting that genes located in the short arm of chromosome 6 may not be relevant in the immune response toward infection with C. carrionii in this Venezuelan endemic zone. Deleted MICA alleles on HLA-B*4802 haplotypes were present among several members of the extended family, but only two of them were affected.
Assuntos
Ascomicetos/imunologia , Cromoblastomicose/imunologia , Antígenos HLA/imunologia , Haplótipos , Antígenos de Histocompatibilidade Classe I/imunologia , Alelos , Cromoblastomicose/genética , Segregação de Cromossomos , Feminino , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , LinhagemRESUMO
The genetic variation at the Apolipoprotein E locus (APOE) is an important determinant of plasma lipids and has been implicated in various human pathological conditions. The objective of the present study was to estimate the distribution of APOE alleles in five Venezuelan communities: two Amerindian tribes (Bari and Yucpa), one Negroid population from Curiepe, one Caucasoid population from Colonia Tovar and the Mestizo urban population living in Caracas. The APOE*3 allele was the most common allele in all populations studied. However, a significant increase in the APOE*2 allele frequency in the Mestizo (18.96%) and Negroid (16.25%) populations was found. Similar to results reported in other Native American populations we have found that the APOE*2 allele is completely absent in the Bari and Yucpa Amerindians. Frequencies found in the Colonia Tovar population are in agreement with those reported in the population of Germany, indicating a high degree of relatedness. The results support the notion that the distribution of the APOE alleles shows ethnic variability.
Assuntos
Apolipoproteínas E/genética , Polimorfismo Genético , Alelos , Frequência do Gene , Humanos , Grupos Populacionais/genética , Venezuela/etnologiaRESUMO
Among the several hypothesis postulated to explain the pathogenesis of severe dengue disease, the model of immunopathogenesis is the most supported one with a likely important role played by the cascade of cytokines. This work describes single-nucleotide polymorphism of tumor necrosis factor (TNF)-alpha, interferon-gamma, interleukin (IL)-6, transforming growth factor-beta1, and IL-10 in patients with dengue virus infections and analyzes their relation with clinical manifestations of the disease. Because cytokine gene polymorphisms affect cytokine production, the significant increase of the TNF-308A allele we have observed among patients with dengue fever (DF) with hemorrhagic manifestations compared to patients with DF only indicates that the former patients are genetically predisposed to express higher levels of TNF-alpha. This finding supports studies reporting a possible association between elevated levels of circulating TNF, vascular permeability, and hemorrhage in patients with dengue hemorrhagic fever.
Assuntos
Alelos , Citocinas/genética , Dengue Grave/genética , Fator de Necrose Tumoral alfa/genética , Fatores de Necrose Tumoral/genética , Citocinas/metabolismo , Vírus da Dengue/metabolismo , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Polimorfismo Genético , Fator de Necrose Tumoral alfa/metabolismo , Fatores de Necrose Tumoral/metabolismoRESUMO
Investigated were two CCR5 gene polymorphisms, the CCR5 Delta 32 deletion and the pCCR5 59029 A-->G promoter point mutation, in 107 ethnically mixed Venezuelan patients serologically positive for Trypanosoma cruzi (34 asymptomatic, 38 arrhythmic, 35 cardiomyopathic). No difference in the distribution of CCR5 Delta 32 among asymptomatic and symptomatic patients was found. We have observed an increase of the 59029-G phenotype among asymptomatic compared with symptomatic chagasic patients (68% vs. 58%), in agreement with previously reported data (57% vs. 31%). This frequency difference, although not statistically significant, is more marked when the 59029-G allele is present in homozygous form. However, a similar distribution of the G/G genotype is present among asymptomatic patients and patients with heart failure. Because it has been reported that the 59029G/G genotype associates with lower CCR5 expression, 37% of our T. cruzi-infected patients with heart failure are genetically predisposed to express low levels of CCR5 on the surface of CD8(+) T cells, contrary to what would be expected if an inflammatory response is required for severe cardiac damage. If confirmed, the possible protection that might be conferred by the G/G genotype may be due to the existence of other genes in linkage disequilibria.
Assuntos
Cardiomiopatia Chagásica/genética , Doença de Chagas/genética , Receptores CCR5/genética , Animais , Cardiomiopatia Chagásica/diagnóstico , Doença de Chagas/etnologia , Doença de Chagas/parasitologia , DNA/genética , DNA/isolamento & purificação , Eletroforese em Gel de Ágar , Frequência do Gene/genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Fenótipo , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Trypanosoma cruzi/imunologia , VenezuelaRESUMO
Previous studies have shown that infection with the protozoan Trypanosoma cruzi (Chagas' disease) is associated with genetic components [human leukocyte antigen (HLA) genes and T-cell receptor (TCR) genes]. We studied the TCR Vbeta repertoire of peripheral blood lymphocytes of 23 unrelated serologically positive subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The patients, previously tested for HLA genotypes, were clinically classified as asymptomatic, arrhythmic and cardiopathic patients. Statistical analysis showed the significant increment of the Vbeta7 family in chagasics with arrhythmia compared with asymptomatic and cardiopathic patients, indicating that the frequency of this family is variable in different clinical forms of the disease and possibly that these T cells might be a marker of the progression of Chagas' disease. Based on the calculation of a Delta score the order of variability in the TCR repertoire was: patients with heart failure > asymptomatic > arrhythmic patients. The major histocompatibility complex (MHC) of the individual may influence the use of particular V genes in T-cell response to foreign antigens. We found a significant increase of the Vbeta7 family in arrhythmic patients who were DRB1*01 DQB1*0501 DPB1*0401, a marker associated with susceptibility to cardiac damage in Chagas' disease. If confirmed by further studies in a larger cohort, a possible association between the TCR Vbeta repertoire and the MHC haplotype of chagasic patients could be postulated.