Association of a TNF?? Gene Polymorphism with Complications After Major Abdominal Operations

Abstract

In injured patients, it has been shown that a polymorphism of the tumor necrosis factor-beta (TNFbeta) gene is related to the development of sepsis. We investigated the relation of TNFbeta gene polymorphism with the development of severe complications after elective major abdominal operations, and with production of TNFalpha perioperatively. In the present investigation, the Ncol polymorphism was studied in genomic DNA isolated from the blood of 172 patients. Preoperatively and postoperatively, lipopolysaccharide (LPS)-stimulated production of TNFalpha in the patients' whole blood was tested in vitro. Genotypes and TNFalpha production were related to the occurrence of severe complications. Postoperatively, 15% (n = 26) of the patients developed severe complications. The overall mortality was 2% (n = 3). The homozygous TNFB2 genotype was found in 54% of the patients, the homozygous TNFB1 genotype was found in 14% of the patients, and the heterozygous genotype was found in 32% of the patients. In patients with complications, the B2B2 genotype was much more frequent (21/26, 81%) than in those without complications (72/146, 49%; P < 0.003). The development of complications was associated with a lower capacity to produce TNFalpha 3 and 7 days after the operation. In patients without complications, the TNFbeta polymorphism was not related to different levels of TNFalpha production. These data indicate an association between TNFbeta polymorphism and postoperative complications and they suggest the B2/B2 genotype as a high risk factor for the development of sepsis after elective operative trauma.

−308GAandTNFBpolymorphisms in acute respiratory distress syndrome

“…Given the small number of -308A homozygotes, homozygotes for the -308A allele were grouped with the heterozygotes (-308A), and compared with -308G homozygotes in the final model, as in prior reports [15,16]. As the distribution of the TNFB genotype among cases and controls did not clearly suggest a dominant or recessive model, the TNFB genotype was modelled as in previous reports [17,18] by comparing TNFB2 homozygotes (TNFB22) with homozygotes and heterozygotes for TNFB1. C-statistics (area under the receiver operating characteristic curve) were used to evaluate model fit [27].…”

“…Carriers of the -308A allele (-308A) and homozygotes for the TNFB2 allele (TNFB22) have increased TNF-a production [14,15] and increased susceptibility to, or increased mortality in, septic shock in some studies [15][16][17][18][19], but not in others [20,21].…”

Perioperative Gene Expression Analysis for Prediction of Postoperative Sepsis

“…Although earlier concepts of the pathophysiology of sepsis regarded these cytokines mainly as mediators of shock and cell damage, newer findings have demonstrated that a certain level of production of these cytokines is necessary for a patient to survive sepsis. In this context, Riese et al found an association between complications and a postoperatively reduced capacity of macrophages to secrete cytokines (23 ).…”

Too much lactate or too little liver?

“…At some point in the future, patients may receive preoperative genetic screening to predict their susceptibility to perioperative lactic acidosis and other surgical complications. 41 …”