RESUMO
Post-transplant diabetes mellitus (PTDM) is a metabolic disorder occurring after solid organ transplantation during the therapy with calcineurin inhibitors. ATP-sensitive potassium channels KCNJ11 and KCNQ1 play an important role in the regulation of insulin secretion by ß cells and development of diabetes mellitus. Numerous studies have confirmed the association between KCNJ11 and KCNQ1 gene polymorphisms and type 2 diabetes. The aim of this study was to examine the association between KCNJ11 and KCNQ1 gene polymorphisms and posttransplant diabetes mellitus in kidney allograft recipients treated with tacrolimus. The study included 201 patients who received kidney transplants. The patients were subdivided into two subgroups: patients with PTDM (N = 35) and patients without PTDM (N = 166). The association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes was studied in three models of univariate Cox regression analysis, i.e., additive, dominant and recessive. In these three models there were no statistically significant associations between KCNJ11 and KCNQ1 gene polymorphisms and PTDM. The results of this study suggest lack of association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes mellitus in kidney allograft recipients treated with tacrolimus in the Polish population.
Assuntos
Canal de Potássio KCNQ1/genética , Transplante de Rim/métodos , Polimorfismo Genético/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Tacrolimo/uso terapêutico , Adulto , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cyclosporin A and sirolimus are becoming commonly used in immunosuppressive treatment in organ transplant patients. The drugs are both metabolized by cytochrome P450 3A4 and are substrates of P-glycoprotein. Thus, interaction between these drugs is possible. The case reported here illustrated that clinicians should be aware of this important drug-drug interaction.
Assuntos
Ciclosporina/uso terapêutico , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Sirolimo/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Ligação Competitiva , Ciclosporina/farmacocinética , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Sirolimo/imunologia , Transplante HomólogoRESUMO
INTRODUCTION: Proinflammatory cytokines have been implicated in the pathogenesis of acute kidney allograft rejection. The aim of the study was to examine the association between interleukin (IL)-2 -330 and tumor necrosis factor (TNF)-alpha -308 promoter polymorphisms and acute kidney allograft rejection. METHODS: The study included 72 patients with long-term stable graft function, and 57 diagnosed with acute kidney allograft rejection. RESULTS: Patients with acute kidney allograft rejection showed a prevalence of subjects with TNF-alpha T2 allele (P < .05). The risk of acute kidney allograft rejection diagnosis was 2.5-fold greater among carriers of the T2 allele than those homozygous for T1T1 (OR 2.53, 95% CI 1.19 to 5.37, P < .05) There was no statistically significant difference in the distribution of IL-2 genotypes between patients with stable graft function and acute kidney allograft rejection. CONCLUSION: The results suggest that TNF-alpha-308 promoter polymorphism is a risk factor for acute kidney allograft rejection.
Assuntos
Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/genética , Interleucina-2/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , Doença Aguda , Triagem de Portadores Genéticos , Genótipo , Sobrevivência de Enxerto/genética , Homozigoto , Humanos , Transplante de Rim/imunologia , Polimorfismo de Fragmento de Restrição , Deleção de SequênciaRESUMO
Chronic allograft rejection remains an important cause of morbidity after kidney transplantation. The aim of the study was to examine the association between IL-2, IL-6 and TNF-alpha promoter polymorphisms and chronic kidney allograft rejection. The study included 64 patients with long-term stable graft function and 62 with chronic allograft nephropathy. Among patients with chronic allograft nephropathy a statistically significant prevalence of the IL-6 CC genotype associated with low IL-6 expression was observed (p < 0.01, OR 3.18; 95% CI 1.27-8.15). There were no statistically significant differences in distribution of IL-2 and TNF-alpha genotypes between patients with stable graft function and chronic allograft rejection. The results of present study suggest that the genetically determined low IL-6 production may be the risk factor of chronic allograft nephropathy development.
Assuntos
Citocinas/genética , Rejeição de Enxerto/genética , Transplante de Rim , Doença Crônica , Citocinas/metabolismo , Rejeição de Enxerto/imunologia , Humanos , Interleucina-2/genética , Interleucina-2/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Polimorfismo Genético , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The FcgammaRIIa receptors, which provide a crucial link between cellular and humoral components of the immune response, display allelic polymorphism. Individuals are homozygous for either arginine 131 (RR131) or histidine 131 (HH131) or are heterozygous for these two alleles (RH131). The HH131 genotype binds human IgG2 with high RR131 with low, and RH131 with intermediate affinity. The aim of the study was to evaluate the FcgammaRIIa polymorphism in patients with chronic kidney graft rejection. The study included 121 renal transplant recipients: 53 patients with long-term stable graft function and 68 with chronic allograft rejection. The distribution of FcgammaRIIa genotypes in patients with chronic kidney graft rejection did not differ significantly from that in patients with stable graft function. The results suggest that the FcgammaRIIa polymorphism is not an important genetic risk factor for chronic rejection of kidney allografts.
Assuntos
Antígenos CD/genética , Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Polimorfismo Genético , Receptores de IgG/genética , Adulto , Sequência de Bases , Primers do DNA , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante HomólogoRESUMO
OBJECTIVE: The N-acetyltransferase polymorphism is involved in the metabolism of many xenobiotics, as well as in susceptibility to some diseases such as rheumatoid arthritis (RA). The aim of this study was to investigate the influence of NAT 2 polymorphism on disease activity in RA patients. METHODS: 70 with RA were enrolled in the study. As a measure of disease activity, the number of swollen and tender joints, the duration of morning stiffness, ESR and CRP as well as disease activity based on a global physician's assessment were evaluated. The NAT2 polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: The mean number of swollen and tender joints, as well as the ESR and CRP values, did not differ significantly with the acetylation genotype. Erosive RA was diagnosed in 74.5% of the slow and 40% of the fast acetylators. The risk for the development of erosive RA was 4.39 time greater in slow acetylators than in fast acetylators. CONCLUSION: NAT2 polymorphism may be a genetic risk factor for joint destruction.
Assuntos
Artrite Reumatoide , Arilamina N-Acetiltransferase/genética , Predisposição Genética para Doença , Polimorfismo Genético , Acetilação , Adulto , Idoso , Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Feminino , Humanos , Articulações/fisiopatologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Índice de Gravidade de DoençaRESUMO
The Fc gamma RIIa receptors are the most widely distributed of the three classes of Fc receptors and expresses an allelic polymorphism. This polymorphism may modulate the immune response and may be a factor for some diseases. The aim of the study was to evaluate the association between the Fc gamma RIIa polymorphism and acute kidney graft rejection. The study was carried out in 115 kidney allograft recipients. The frequency of acute kidney graft rejection was similar in relation to Fc gamma RIIa genotypes. We suggest that Fc gamma RIIa polymorphism is not important risk factor for acute kidney graft rejection susceptibility.