RESUMO
Genetic and nongenetic factors are involved in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). The best-known genetic factor for susceptibility to IMIDs is the human leukocyte antigen (HLA). The aim of the present study was to evaluate the association of HLA class II genes with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) in the Paraguayan population. We included 254 patients with IMIDs (101 SLE, 103 RA, and 50 SSc) and 50 healthy controls. The haplotypes of five genes corresponding to HLA class II genes and their relationship to the IMIDs studied were determined. Note that 84.6% were women, with a mean age of 43.4 ± 14 years. Among the associated HLA alleles, we found the previously identified risk factors in other populations like HLA-DRB1*03:01 and HLA-DRB1*14:02 for RA, as well as new ones not previously identified, such as DPA1*02:01 for SLE and, DB1*02:01 for RA and SSc. In the genetic association analysis, already known associations have been replicated, and unpublished associations have been identified in Paraguayan patients with IMIDs. This is the first genetic association study in Paraguayan patients with IMIDs.
Assuntos
Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Predisposição Genética para Doença , Alelos , Agentes de Imunomodulação , Lúpus Eritematoso Sistêmico/genética , Cadeias HLA-DRB1/genética , Artrite Reumatoide/genética , HaplótiposRESUMO
El estado mutacional del KRAS ha sido considerado como biomarcador para tratamientos biológicos tras varios ensayos clínicos realizados en pacientes con cáncer colorrectal metastásico. Reportes recientes indican que las frecuencias de mutación del gen KRAS en pacientes con CCR de Asia, Europa y Latinoamérica están entre el 24%, 36% y 40%, respectivamente. Paraguay no cuenta con este tipo de informes, a pesar de registrar anualmente en promedio 75 nuevos casos de pacientes diagnosticados con CCR sólo en el Servicio de Cirugía General del Hospital Central del Instituto de Previsión Social (IPS). El presente trabajo ha implementado este análisis de rutina, prerrequisito obligatorio para la administración de fármacos basados en anticuerpos terapéuticos, y revelado una frecuencia de mutación del gen KRAS del 34% en pacientes paraguayos con CCR que acuden a los Servicios del Hospital Central del IPS
The mutational status of the KRAS has been consider as a biomarker for biological treatments after several clinical trials carried out in patient with metastatic colorectal cancer. Recent reports indicate that the KRAS gene mutation frequencies in CRC patients from Asia, Europe, and Latin America are between 24%, 36%, and 40%, respectively. Paraguay does not have this kind of reports, despite registering an average of 75 new cases of patients diagnosed with CRC per year only in the General Surgery Service of the "Central Hospital - Instituto de Prevision Social (IPS)". The present work has implemented this routine analysis, a mandatory prerequisite for the administration of drugs based on therapeutic antibodies and revealed a KRAS gene mutation frequency of 34% in Paraguayan patients with CRC who attend the IPS Central Hospital Services
Assuntos
Neoplasias Colorretais , Mutação , Estudos Transversais , GenesRESUMO
We report a new germline mutation in exon 13 of the hMSH2 gene (c.2081T>C; F694S) in a patient diagnosed with colorectal carcinoma. The patient's family fulfilled the clinical criteria of the Bethesda guidelines for Lynch syndrome. The segregation analysis determined the presence of the mutation in the proband's mother (breast cancer younger than 40 years old) and in two healthy daughters. The mutation was not present in 116 normal controls screened. The medical implications for the carrier relatives are discussed.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa , Proteína 2 Homóloga a MutS/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Espanha , População BrancaRESUMO
The ultimate goal of cancer proteomics is to adapt proteomic technologies for routine use in clinical laboratories for the purpose of diagnostic and prognostic classification of disease states, as well as in evaluating drug toxicity and efficacy. The novel technologies allows researchers to facilitate the comprehensive analyses of genomes, transcriptomes, and proteomes in health and disease. The information that is expected from such technologies may soon exert a dramatic change in cancer research and impact dramatically on the care of cancer patients. Analysis of tumor-specific proteomic profiles may also allow better understanding of tumor development and the identification of novel targets for cancer therapy. The localization of gene products, which is often difficult to deduce from the sequence, can be determined experimentally. Mechanisms, such as regulation of protein function by proteolysis, recycling, and isolation in cell compartments, affect gene products, not genes. Finally, protein-protein interactions and the molecular composition of cellular structures can be determined only at the protein level. The biological variability among patient samples as well as the great dynamic range of biomarker concentrations are currently the main challenges facing efforts to deduce diagnostic patterns that are unique to specific disease states. While several strategies exist to address this problem, we have tried to offer a wide perspective about the current possibilities.