Are postoperative complications genetically determined by TNF-beta NcoI gene polymorphism?
BACKGROUND
Postoperative infectious complications are the leading causes for postoperative sepsis. In severe sepsis, tumor necrosis factor-beta (TNF-beta) NcoI polymorphism was associated with increased mortality. Therefore, the aim of this study was to determine whether the biallelic NcoI polymorphism within the TNF locus is associated with the development of postoperative complications.


METHODS
One hundred sixty patients were included in this prospective observation study. Patients undergoing major gastrointestinal surgery, such as esophagectomy, gastrectomy, Whipple operation, major liver resection, or colon resection were included. Patients were monitored during the clinical course, and postoperative complications, divided into severe and minor complications, were documented. The NcoI restriction fragment length polymorphism of the TNF-beta gene was determined by polymerase chain reaction; gene expression as well as complications were correlated.


RESULTS
The patients' genotype distribution and demographic characteristics were comparable within the different groups of operations. Patients with the heterozygous genotype TNF-beta1/beta2 had a 1.6-fold higher relative risk for developing complications. If patients with the homozygous genotype TNF-beta2 developed a complication, they had a 1.5-fold higher relative risk for severe complications. Furthermore, the mortality of patients with postoperative sepsis who were homozygous for the genotype TNF-beta2 was significantly elevated.


CONCLUSIONS
The TNF-beta NcoI polymorphism influences the development of postoperative complications. While the genotype TNF-beta1/beta2 has a higher risk for developing complications in general, the TNF-beta2/beta2 genotype is associated with more severe complications and mortality from sepsis.
Kahlke
Volker
V
Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller-Strasse 7, 24105 Kiel, Germany.
Schafmayer
Clemens
C
Schniewind
Bodo
B
Seegert
Dirk
D
Schreiber
Stefan
S
Schröder
Jörg
J
D000328:Adult; D000483:Alleles; D013505:Digestive System Surgical Procedures / Q000009:adverse effects*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011183:Postoperative Complications / Q000209:etiology*; D011446:Prospective Studies; D018805:Sepsis / Q000235:genetics*; D012720:Severity of Illness Index
D005819:Genetic Markers; D008233:Lymphotoxin-alpha