Association of a TNFbeta gene polymorphism with complications after major abdominal operations

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.