RESUMEN
BACKGROUND: The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition. OBJECTIVE: We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients. METHODS: Observational, hospital-based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520). RESULTS: The genotypic and allelic frequencies were -308GG = 0.72; -308GA = 0.27; -308AA = 0.01; -308G = 0.85; -308A = 0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients. CONCLUSION: The principal novel input of this study was the larger sample size in an investigation with -308G > A TNF-α SNP. The presence of -308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.
Asunto(s)
Femenino , Humanos , Masculino , Mortalidad Hospitalaria , Insuficiencia Multiorgánica/mortalidad , Polimorfismo Genético/genética , Sepsis/mortalidad , Factor de Necrosis Tumoral alfa/genética , Estudios de Cohortes , Enfermedad Crítica , Frecuencia de los Genes , Genotipo , Insuficiencia Multiorgánica/genética , Fenotipo , Valor Predictivo de las Pruebas , Sepsis/genéticaRESUMEN
Las mitocondrias como organelos subcelulares claves en la generación de la energía son esenciales para la supervivencia de la vida humana. Sus alteraciones conocidas en la actualidad como enfermedades o citopatías mitocondriales se han constituido en la última década en un área de acelerado desarrollo que involucra a todas las especialidades de la medicina. Focos de estudio de especial interés son la herencia "no tradicional" de estos trastornos con un doble control genético (nuclear y mitocondrial); la expresión variable de estas enfermedades en distintos tejidos (multisistémicas o multitisulares) y el creciente diagnóstico de estos cuadros que parecen ser más frecuentes.