Genetics polymorphisms (SNPs) for susceptibility to and outcome of sepsis

• Grant number: 05/02041-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2006
• End date: April 30, 2008
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Eloiza Helena Tajara da Silva
• Grantee: Eloiza Helena Tajara da Silva
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

The sepsis is one important problem of public health in intensive care units in Brazil, with an incidence density about 57 per 1000 patient-days and mortality rate of 51,6% and 57,1% in patients wth severe sepsis and septic shock, respectively. Although technologic, pharmacologic, and surgical advances have improved the outcomes of many diseases, the mortality of septic shock continues to be distressingly high. Different genetic epidemiologic studies suggest a strong genetic influence on the outcome from sepsis, and genetics may explain the wide variation in the individual response to infection. Several candidate genes have been identified as important in the inflammatory response and investigated in case-controlled studies, including the tumor necrosis factor TNFalpha and TNFbeta; genes, positioned next to each other within the cluster of human leukocyte antigen class III genes on chromosome 6. Other candidate genes for sepsis and septic shock include interleukin IL1 receptor antagonist, heat shock protein HSP70, IL-6, IL-10, CD-14, Toll-like receptor (TLR4), TLR-2 and anexin A1 (ANXA1). In the present study, polymorphisms in these genes will be investigated using real-time polymerase chain reaction assay and specific fluorescence-labeled probes or electrophoresis-based genotyping system. Patients suffering from sepsis, severe sepsis and septic shock and healthy volunteers matched for sex, gender and ethnicity will be included in this study.This project was designed to study polymorphisms and to identify evidences for a genetic susceptibility to development of sepsis and death from sepsis. The data may be useful for identifying therapeutic targets. (AU)