Effect of epigenetics on rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune and inflammatory disease that predominantly affects the diarthrodial joints. In this pathology, environmental or behavioral factors can act in synergy with genetic predisposition, accelerating the onset and severity of the disease. This link between the environment and the genome is mediated by epigenetic marks on deoxyribonucleic acid, including its methylation, histone modification, and noncoding ribonucleic acid-mediated regulation.

Role of HLA-DQB1 alleles in the risk, signs and symptoms, and severity of celiac disease in a Venezuelan population.

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.

Polymorphisms of the TLR4 gene: Risk factor for chronicity and severity in oral vectorial Chagas disease.

Chagas disease is one of the parasitic infections with the greatest socio-economic impact in Latin America. In Venezuela, epidemiological data has shown different sources of infection, such as the vectorial route by oral transmission. Given the importance of the TLR4 gene in the innate immune response triggered by infection with Trypanosoma cruzi, this work analyses the role of TLR4 polymorphisms and its possible effect on cytokine expression.

[Polimorfismo de genes de citocinas: ¿factores de riesgo cardiovascular en la población venezolana?].

Objective: To examine whether the polymorphisms of the IL6, TNFA and IL10 genes represent a risk marker for acute myocardial infarction (AMI) and to analyze their correlation with risk factors, age of occurrence and type of AMI.

Method: Association study that included 310 unrelated Venezuelan individuals, grouped in 190 patients with AMI and 120 controls with or without cardiovascular risk factors. The IL6-174 G/C (rs1800795), TNFA -308 G/A (rs1800629), and IL10-1082 A/G (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms were determined using the polymerase chain reaction technique with sequence-specific primers.

Genetic variability of molecules involved in the disease pathogenesis in Leishmania infection.

Macrophages are the primary host cell for Leishmania parasites, by Toll like receptors (TLR-MyD88) that are central components of the innate and adaptive immunity against leishmania infection. The CD40/CD40L interaction has also been shown to be important in resistance to various protozoa. In this context, one of the most important properties of suppressors of cytokine signalling (SOCS) proteins, especially SOCS1 and SOCS3, is the regulation of macrophages cell for Leishmania parasites.

[Study of the association between the polymorphism of the TNF-α gene and prostate cáncer].

Background: Prostate cancer is the third cause of cancer death in men in the Western hemisphere and the second cause of cancer death in Zulian men from Venezuela.

Objective: To determine whether polymorphisms 308 and 238 of the tumor necrosis factor alpha (TNF-α) gene are associated with prostate cancer.

Methods: The DNA that was extracted from the peripheral blood of 40 patients with prostatic specific antigen and 40 controls was amplified by PCR plus digestion with enzymes NcoI and MspI.

Postprandial Hypertriglyceridemia Is Associated with the Variant 54 Threonine Gene.

Fasting or postprandial hypertriglyceridemia is considered an independent cardiovascular disease (CVD) risk factor. The intestinal fatty acid binding protein (FABP2) is involved in the intracellular transport and metabolism of fatty acids. The presence of the polymorphism of the gene appears to be involved in postprandial hypertriglyceridemia.

NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population.

Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis.

Role of genes GSTM1, GSTT1, and MnSOD in the development of late-onset Alzheimer disease and their relationship with APOE*4.

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.

The role of haptoglobin genotypes in Chagas disease.

Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease.

Distribution of killer cell immunoglobulin-like receptor genes in the mestizo population from Venezuela.

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.

Influence of CTLA-4 gene polymorphism in autoimmune and infectious diseases.

Cell-mediated immunity requires costimulatory activity to initiate or inhibit antigen-specific T-cell responses. CTLA-4 is an inhibitory receptor expressed by activated and regulatory T cells. The single nucleotide polymorphism (SNP) +49 A/G of the CTLA-4 gene alters intracellular distribution of CTLA-4, interleukin-2 production, and, as a consequence, T-cell proliferation.

Genetic contribution of major histocompatibility complex class II region to type 1 autoimmune hepatitis susceptibility in Venezuela.

Aims: Autoimmune hepatitis (AIH) is a progressive liver disease characterized by the presence of circulating autoantibodies, hypergammaglobulinaemia and a favourable response to immunosuppressive treatment. Although the pathogenesis of type 1 AIH is unknown, disease susceptibility is partially determined by genes linked to the class II region of the major histocompatibility complex. Type 1 AIH has been associated with DRB1*03, DRB1*04 and DRB3 alleles in European and North American Caucasians, with DRB1*0405 in Japanese, with DRB1*0404 in Mexican, and with DRB1*1301 in Argentinean populations.

HLA-DRB1*0402 haplotypes without DQB1*0302 in Venezuelan patients with pemphigus vulgaris.

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.

Human leukocyte antigen class I and MICA haplotypes in a multicase family with Cladophialophora carrionii chromoblastomycosis.

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.

Genetic polymorphisms at four STR loci from the HLA region in a Venezuelan population.

Whole blood samples from 74 unrelated healthy individuals were collected. The donors' sample included Venezuelan mestizos from various regions of the country, but mostly from the resident population of Caracas City. A Venezuelan mestizo is the offspring of a mating between a native Venezuelan and a person born in Europe, mainly in Spain.

Genetic variability of Apolipoprotein E in different populations from Venezuela.

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.

TNF-alpha-308A allele, a possible severity risk factor of hemorrhagic manifestation in dengue fever patients.

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.

Is the CCR5-59029-G/G genotype a protective factor for cardiomyopathy in Chagas disease?

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.

HLA class II and class I polymorphism in Venezuelan patients with myasthenia gravis.

Oligotyping performed among ethnically mixed Venezuelan patients with myasthenia gravis (MG) and controls has revealed positive associations of HLA class I A*31, B*08, B*39, B*40, C*15, C*17, and class II DRB1*09 and negative associations of DQB1*06 and DQA1*02 with the disease. Sequential removal of human leukocyte antigen B (HLA-B) alleles when relative predispositional effects (RPEs) were looked for demonstrated that B*08 is the allele group with the largest contribution in the overall MG patients followed by B*39 and B*40. Several specificities (A*31, B*08, C*17, DRB1*03, DQA1*05, and DQB1*02) indicated increased frequencies among patients with thymic hyperplasia versus patients without hyperplasia or controls.

Synthesis, characterization, DNA binding study and biological activity against Leishmania mexicana of [Cu(dppz)2]BF4.

[Cu(dppz)(2)]BF(4) complex has been synthesized by the reaction of [Cu(CH(3)CN)(4)]BF(4) and dipyrido[3,2-A:2',3'-c]phenazine (dppz) in a molar ratio of 1:2. The compound was characterized by fast atom bombardment mass spectrometry, 1H nuclear magnetic resonance, UV-Vis and IR spectroscopies. Absorption and viscometric studies carried out on the interaction of [Cu(dppz)(2)]BF(4) complex with calf thymus DNA suggested that the complex binds by intercalation.

Design of copper DNA intercalators with leishmanicidal activity.

The complexes [Cu(dppz)(NO(3))]NO(3) (1), [Cu(dppz)(2)(NO(3))]NO(3) (2), [Cu(dpq)(NO(3))]NO(3) (3), and [Cu(dpq)(2)(NO(3))]NO(3) (4) were synthesized and characterized by elemental analysis, FAB-mass spectrometry, EPR, UV, and IR spectroscopies, and molar conductivity. DNA interaction studies showed that intercalation is an important way of interacting with DNA for these complexes. The biological activity of these copper complexes was evaluated on Leishmania braziliensis promastigotes, and the results showed leishmanicidal activity.

Analysis of the T-cell receptor beta-chain variable-region (Vbeta) repertoire in chronic human Chagas' disease.

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.

Influence of the HLA class II polymorphism in chronic Chagas' disease.

Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol.