RESUMEN
The two polymorphisms [IL-12 (-1188) A/C and the IFN-γ (+874) A/T)] are known to have functional consequences and henceforth were analyzed in subacute sclerosing panencephalitis (SSPE) patients to reveal a possible relation with these polymorphisms and this debilitating disease. For the IL-12 (-1188) A/C polymorphism, 78 patients and 90 healthy individuals were analyzed. An increase in the AA genotype was determined (p = 0.02, OR = 2.06). There was also a statistically significant difference between the control group and the patients with respect to the allele frequencies (p = 0.04, OR = 1.65). For the IFN-γ (+874) A/T polymorphism, 69 SSPE patients and 115 controls were studied and there was not a significant difference between the two groups. Our findings suggested that not the IFN-γ (+874) A/T but the IL-12 (-1188) A/C polymorphism is correlated with SSPE and having an AA genotype or A allele decreases the risk of developing SSPE by 2.06- and 1.65-fold, respectively.
Asunto(s)
Genotipo , Interferón gamma/genética , Interleucina-12/genética , Virus del Sarampión/patogenicidad , Polimorfismo de Nucleótido Simple , Panencefalitis Esclerosante Subaguda/genética , Alelos , Estudios de Casos y Controles , Expresión Génica , Frecuencia de los Genes , Humanos , Interferón gamma/inmunología , Interleucina-12/inmunología , Virus del Sarampión/inmunología , Regiones Promotoras Genéticas , Factores Protectores , Panencefalitis Esclerosante Subaguda/inmunología , Panencefalitis Esclerosante Subaguda/patología , Panencefalitis Esclerosante Subaguda/virologíaRESUMEN
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface protein, which down-regulates the immune response at CTLA-4/CD28/B7 pathway. We aimed to investigate the influence of the -318 C/T, +49 A/G, -1661 A/G and CT60A/G, and CTLA-4 gene polymorphisms on acute rejection of kidney allograft in Turkish patients. The study design was a case-control study that consists of three groups: Group 1 (n = 34) represented the kidney transplant (Ktx) recipients who experienced acute rejection, Group 2 (n = 47) was randomly assigned Ktx recipients without acute rejection, and Group 3 (n = 50) consisting of healthy volunteers to evaluate the normal genomic distribution. The polymerase chain reaction-restriction fragment length polymorphism technique was used to determine the polymorphisms. Genotype and allele frequencies among three groups denoted similar distributions for +49 A/G, -1661 A/G, and CT60A/G. Conversely, -318 C/T genotype was three times more frequent in the acute rejection group than in the non-rejection group (OR = 3.45; 95%CI = 1.18-10.1, p = 0.015) and two times more frequent than the healthy control group (OR = 2.45; 95% CI = 0.98 - 6.11, p = 0.047). Additionally, having a T allele at -318 position was significantly associated with acute rejection (0.147 vs. 0.043, OR = 3.45; 95% CI = 1.13-10.56, p = 0.02). 318C/T gene polymorphism and T allelic variant were found to be associated with increased acute rejection risk in Turkish kidney allograft recipients.
Asunto(s)
Antígeno CTLA-4/genética , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/genética , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Polimorfismo de Nucleótido Simple/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Aloinjertos , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Genotipo , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Turquía , Adulto JovenRESUMEN
Behçet's disease (BD) is a systemic, autoinflammatory, chronic disorder which affects various parts of the body in genetically susceptible individuals. BD has a multi-factorial etiopathogenesis which encompasses both innate and adaptive arms of immunity. NK cells, which kill virus-infected or malign cells and provide interaction between adaptive and innate immune system, are also known to involve in the pathogenesis of autoimmune/autoinflammatory diseases including BD. NK cells function in immune responses via the signals obtained from surface-expressed activating and inhibitory receptors. In this study, we aimed to explore NK cell activation status by measuring the levels of activation marker CD69 and activating receptors NKG2D, NKp30, and NKp46 as well as proliferative and cytotoxic capacities in response to stimulation with interleukin (IL)-15-combined cytokines in BD patients. CD4+ and CD8+ T cell responses were also evaluated to compare with those of NK cells. As a result, the expression of activating receptors on NK cells was demonstrated to be varied among patients with active and inactive BD and healthy controls. The proliferation levels of NK cells were elevated in BD patients, especially in inactive phase of disease compared to healthy controls. Additionally, CD107a levels of inactive BD patients were detected to be lower in comparison with healthy controls and active BD patients. These findings suggest that BD patients in active and inactive phases display different activation status of NK cells which indicate NK cells might be associated with immune attacks and remissions during the course of BD.
Asunto(s)
Síndrome de Behçet , Citocinas/metabolismo , Humanos , Interleucina-15/metabolismo , Células Asesinas Naturales , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismoRESUMEN
Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal disease caused by reactivation of a mutated measles virus in brain tissue. The process of reactivation is yet to be elucidated. In this study, the possible roles of the Th1 (interleukin [IL]-12, interferon [IFN]-γ) and the Th17 axis (IL-23, IL-17, IL-22), particularly of IL-17, in the pathogenesis of SSPE were investigated. Briefly, mononuclear cells from SSPE patients were stimulated using measles virus peptide, and the release of IL-12, IL-23, IL-22, IFN-γ, and IL-17 cytokines was measured using enzyme-linked immunosorbent assay and/or enzyme-linked immunosorbent spot assay (ELISpot). We found that in comparison to the mononuclear cells obtained from healthy donors, cells from SSPE patients exhibited increased levels of IL-12, IL-23, IL-17, IL-22, and IFN-γ cytokines in response to measles virus stimulation. However, the same result was not obtained with cytomegalovirus and phytohemagglutinin. Using flow cytometry, mononuclear cells obtained from SSPE patients and healthy controls were also analyzed for the presence of intracellular IL-17 in response to measles virus stimulation. On stimulation, the number of IL-17-positive cells were found to be higher among mononuclear cells obtained from the patients. In addition, the numbers of IL-17- and IFN-γ-positive cells were significantly increased in SSPE patients. In conclusion, this study demonstrates that both the IL-12/IFN-γ and the IL-23/IL-17/IL-22 pathways are functionally abnormal in SSPE pathogenesis. Targeting these pathways and their specific pro-inflammatory mediator production may provide a new strategy to suppress SSPE development.
Asunto(s)
Interferón gamma/metabolismo , Interleucinas/metabolismo , Panencefalitis Esclerosante Subaguda/inmunología , Adolescente , Niño , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Virus del Sarampión/inmunología , Panencefalitis Esclerosante Subaguda/tratamiento farmacológico , Proteínas Virales/inmunologíaRESUMEN
Interferon-gamma is the most important cytokine in resistance to mycobacterial diseases and common variants of interferon-gamma gene could be related to tuberculosis susceptibility. We tested the hypothesis that the interferon-gamma+874T-A polymorphism is associated with tuberculosis disease, and affects the interferon-gamma response. We determined by pyrosequencing the distribution of the interferon-gamma+874T-A polymorphism in a Turkish population of 319 patients with pulmonary tuberculosis, 42 children with severe forms of tuberculosis and 115 healthy donors. We also analysed whether any correlation exists between this polymorphism and interferon-gamma response to Mycobacterium tuberculosis antigens by ELISPOT in 58 pulmonary tuberculosis cases, and the results were analysed according to the genotypes. We found that the minor allele (T) frequency was significantly lower in patients with pulmonary tuberculosis when compared to controls (P=0.024, OR=0.7), a similarly significant decrease in the frequency of TT genotype was observed in patients with pulmonary tuberculosis, compared to the control group (P=0.02, OR=0.49). IFN-gamma responses to PPD antigen in TT genotype was found to be significantly higher than the AA group (P>0.001). Non-parametric correlation analysis of ELISPOT data showed significant reverse correlation in PPD, CFP10 and ESAT6 values and IFN-gamma +874 genotypes. These results show that the IFN-gamma +874T-A polymorphism is related to the IFN-gamma response and the magnitude of the response decreases during transition from TT- to TA and to AA genotypes. Our data suggest that similar to various Caucasian populations, in a Turkish population the IFN-gamma+874 T-A polymorphism is also associated with tuberculosis disease and affects the magnitude of the IFN-gamma response.
Asunto(s)
Interferón gamma/genética , Tuberculosis Meníngea/genética , Tuberculosis Miliar/genética , Tuberculosis Pulmonar/genética , Adulto , Antígenos Bacterianos , Niño , Expresión Génica/fisiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Inmunoensayo , Lactante , Mycobacterium tuberculosis/inmunología , Turquía , Población BlancaRESUMEN
BACKGROUND: Genetic factors that predispose individuals to pemphigus are considered to play important roles in the development of the disease. Furthermore, population studies of patients with pemphigus have clearly shown that the most prevalent alleles differ across ethnic groups. OBJECTIVES: This controlled study was designed to detect the distribution of human leukocyte antigen (HLA) class I and II alleles in Turkish patients with pemphigus. METHODS: Sixty patients diagnosed with pemphigus according to clinical findings, histology, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were enrolled in the study. The control group consisted of 60 healthy adult transplant donors. HLA typing was carried out using a polymerase chain reaction (PCR) with sequence-specific primers (SSP) method. RESULTS: The frequencies of HLAs A*11, CW*01, DRB1*04, DRB1*14, DQB1*05, and DPB1*0401 were found to be statistically significantly higher in the disease group than in controls. By contrast, the frequencies of HLAs B*18, B*50, DRB1*11, DQB1*02, DQB1*06, DPB1*0301, and DPB1*1102 were statistically significantly lower in the pemphigus group than in controls. Linkage dysequilibrium analysis showed that DRB1*14/DQB1*05, A*11/DQB1*05, and A*11/DRB1*14 alleles were detected frequently in pemphigus patients, and DRB1*11/DQB1*05, DRB1*14/DQB1*02, B*50/DQB1*02, and B*50/DPB1*0301 alleles appeared frequently in healthy controls. CONCLUSIONS: The results suggest that DRB1*04, DRB1*14, DQB1*05, and DPB1*0401 class II HLAs and A*11 and CW*01 class I HLAs are associated with pemphigus in southern Turkey. Observed differences in LD patterns between patients and controls suggest that the coexistence of the respective alleles is strongly determinant of predisposition towards (DRB1*14/DQB1*05 and A*11/DQB1*05) or protection against (B*50/DQB1*02) the disease.
Asunto(s)
Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase I/genética , Pénfigo/genética , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Etnicidad/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , TurquíaRESUMEN
Febrile seizures comprise a common type of pediatric convulsion. Inflammation and genetics may be involved in their pathogenesis. Regarding the role of cytokines (especially interleukin-6) in febrile responses, we performed a case control study of interleukin-6 gene (-174, -572, and -597) single-nucleotide polymorphisms to learn if correlations existed between these particular polymorphisms and febrile seizures. We isolated the genomic DNA of 92 children with febrile seizures and 98 healthy control subjects. We genotyped individuals for their polymorphisms, using polymerase chain reaction-restriction fragment length polymorphism. In our study, the frequencies of -174 G alleles and of the -174 and -572 GG genotypes were observed to be significantly higher in patients than in control subjects. The -174 GG genotype frequency was significantly higher in children with a family history of febrile seizures.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Interleucina-6/genética , Polimorfismo Genético/genética , Convulsiones Febriles/genética , Estudios de Casos y Controles , Niño , Preescolar , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lactante , MasculinoRESUMEN
Accumulated data within the recent years demonstrate that reduced levels of VEGF which is a well known angiogenic molecule might cause neurodegeneration in part by impairing neural tissue perfusion, vasoregulation and normal functioning of perivascular autonomic nerves. Additionally, VEGF has been reported to support neuroprotection in dopaminergic neurons by indirect and direct mechanisms and suppress apoptosis in dopaminergic neurons in vitro. The aim of the current study is first to demonstrate whether there is an association between the three common VEGF polymorphisms (-2578C/A, -634C/G and 936C/T) in the VEGF gene and idiopathic Parkinson's disease (IPD) which is a neurodegenerative disease caused by the progressive degeneration of nigrostriatal dopaminergic neurons, and second to see if the serum levels of VEGF is reduced in the patients with IPD. We screened the genotype and allele frequencies of three common functional polymorphisms of VEGF, namely -2578C/A, -634C/G and 936C/T in DNA samples of 126 patients with IPD and healthy control subjects and also we compared the median serum levels of VEGF between these two groups. No association was found between the inspected VEGF polymorphisms and IPD and also no difference was found between the serum VEGF levels of both groups. The current study failed to support the hypothesis that VEGF polymorphisms and/or reduced serum VEGF levels are likely contributors to the neurodegenerative process in IPD.
Asunto(s)
Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Alelos , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. The pro-inflammatory cytokine interleukin-1 (IL-1) has been implicated in the pathogenesis of BD. Our aim was to determine a possible association of specific polymorphisms of IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes with susceptibility for BD. We genotyped 72 patients with BD and 163 healthy controls for IL-1alpha-889, IL-1beta-511, and +3953 (nt5887) single-nucleotide polymorphisms besides IL-1 receptor antagonist variable number of tandem repeat polymorphism (for five different alleles). Comparison of the IL-1beta+3953 T allele and TT genotype frequencies showed a significant difference between patients with BD and controls (54.2 vs. 40.5%, OR = 1.74, P = 0.024, and 40.3 vs. 19.6%, OR = 2.76, P = 0.009, respectively). However, no difference was observed in the genotype or allele frequencies of IL-1alpha-889, IL-1beta-511, and IL-1 receptor antagonist between the patients with BD and the controls. Our results indicate that susceptibility to BD is increased in individuals carrying the IL-1beta+3953 T allele and TT genotype.
Asunto(s)
Síndrome de Behçet/genética , Interleucina-1/genética , Polimorfismo Genético , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , TurquíaRESUMEN
Previous studies suggested that abnormal regulation of TNF-alpha production may have a role in the pathogenesis of rheumatic fever (RF). Polymorphism at the promoter region of TNF-alpha gene (-308 A) has recently been shown to be associated with rheumatic heart disease (RHD) in Mexican patients. Although this polymorphism has long been shown to affect TNF-alpha gene expression in cell lines, its role in production of the cytokine in RF patients has not been studied. We therefore investigated TNF-alpha G-308A single nucleotide polymorphism and its effect on TNF-alpha production in 71 Turkish RF patients and 89 ethnically matched healthy controls. The TNF-alpha-308A allele frequency was found to be significantly higher in RF patients (RHD+arthritis) than in healthy controls [p<0.0032 Odds ratio (OR)=3.4, 95% confidence interval (CI) (1.5-7.7)]. When RHD patients were analyzed as a separate group, significant difference persisted [p<0.0055, OR=3.3, 95% CI (1.5-7.6)]. More importantly, ELISPOT analysis demonstrated that existence of A allele was associated with higher TNF-alpha production compared with G allele. Our data suggest that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop RF disease.