PMID- 12906716 OWN - NLM STAT- MEDLINE DCOM- 20031014 LR - 20220311 IS - 1096-2964 (Print) IS - 1096-2964 (Linking) VI - 4 IP - 2 DP - 2003 Summer TI - Influence of the TNF-alpha and TNF-beta polymorphisms upon infectious risk and outcome in surgical intensive care patients. PG - 163-9 AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-alpha and TNF-beta genes (TNF2 and LTA + 250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-alpha and -beta genes are associated with an increased risk of infection in an at-risk surgical intensive care population. MATERIALS AND METHODS: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing. RESULTS: Eighty-six percent of the patients were TNF1 homozygotes (G:G at -308 of the TNF-alpha promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-beta, whereas the homozygous A:A was present in 45.4% of the patients. CONCLUSION: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock. FAU - Calvano, Jacqueline E AU - Calvano JE AD - Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903, USA. FAU - Um, John Y AU - Um JY FAU - Agnese, Doreen M AU - Agnese DM FAU - Hahm, Sae J AU - Hahm SJ FAU - Kumar, Ashwini AU - Kumar A FAU - Coyle, Susette M AU - Coyle SM FAU - Calvano, Steve E AU - Calvano SE FAU - Lowry, Stephen F AU - Lowry SF LA - eng GR - GM34695/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Surg Infect (Larchmt) JT - Surgical infections JID - 9815642 RN - 0 (Lymphotoxin-alpha) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Aged MH - Base Sequence MH - Critical Care MH - Critical Illness MH - Cross Infection/complications/genetics/immunology MH - Female MH - Genetic Predisposition to Disease/genetics MH - Humans MH - Lymphotoxin-alpha/*genetics MH - Male MH - Middle Aged MH - Polymorphism, Genetic/*genetics MH - Risk MH - Sepsis/etiology/*genetics/immunology MH - Shock, Septic/genetics/immunology MH - Systemic Inflammatory Response Syndrome/genetics/immunology MH - Treatment Outcome MH - Tumor Necrosis Factor-alpha/*genetics EDAT- 2003/08/09 05:00 MHDA- 2003/10/15 05:00 CRDT- 2003/08/09 05:00 PHST- 2003/08/09 05:00 [pubmed] PHST- 2003/10/15 05:00 [medline] PHST- 2003/08/09 05:00 [entrez] AID - 10.1089/109629603766956951 [doi] PST - ppublish SO - Surg Infect (Larchmt). 2003 Summer;4(2):163-9. doi: 10.1089/109629603766956951.