Background Postoperative sepsis remains a challenge for joint care surgeons as it is a significant cause of morbidity and mortality. It has been postulated that genetic factors may have a role and the accurate identification of such risk factors may develop strategies to prevent these potentially devastating catastrophes. Tumor Necrosis Factor (TNF) is believed to be a cytokine central to pathogenesis of sepsis and the TNF-β Nco1 polymorphism has been found to be associated with increased mortality rate in severe sepsis. We postulated that Nco1 polymorphism may be associated with post operative infection in some patients but not in others
Objectives The objective of the study was to analyze TNF- β Nco1 polymorphism in relation to postoperative sepsis outcome in joint care surgeries
Methods The study group consisted of 153 patients undergoing major elective surgery (surgical time more than 1 hour and requiring general anesthesia and or respiratory assistance). Blood samples were obtained for genomic DNA isolation. Genotyping of each patient for TNF- β polymorphism was performed by analyzing restriction fragments of an Nco1-digested DNA fragment obtained using polymerase chain reaction. All the patients were followed for 1 month following surgery for any evidence of sepsis as determined by guidelines from Bone et al. Subjects with and without post-operative infection were compared on presence or absence of polymorphism and of confounder status. Comparison of the proportions gave the odds ratio and odds ratios adjusted for confounders. All the possible confounders were controlled by stratified or regression analysis.
Results The overall allele frequency for TNF-β genotype was 0.32 for TNFB1 and 0.68 for TNFB2. In TNF-β genotype, homozygous recessive TNFB1 were 17 (11.1%), heterozygous TNFB1/TNFB2 were 63 (41.2%) and homozygous dominant TNFB2 were 73 (47.7%). 125 patients showed an uncomplicated postoperative recovery, while 25 developed mild sepsis and 3 developed severe sepsis. Genotype distribution in patients with an uncomplicated clinical course was significantly different from that in patients with postoperative sepsis. Development of postoperative sepsis was significantly higher in patients homozygous for the allele TNFB2. When compared with patients carrying at least one TNFB1 allele (TNFB1 homozygous and heterozygous genotype), the TNFB2 homozygous genotype was associated with an OR of 3.39 (p=0.005; 95% CI 1.4 to 8.3) for the development of severe sepsis. Compared with the heterozygous genotype, the OR for the homozygous TNFB2 genotype was 5.5 (p=0.001; 95% CI 1.78 to 17.33). Although the small number of TNFB1 homozygous surgical patients makes their risk estimate less accurate, the data indicate that both homozygous genotypes possess a significantly increased susceptibility for the development of postoperative sepsis compared with the heterozygous genotype
Conclusions The Nco1 polymorphism within the TNF-β gene influences the development of postoperative sepsis. Both homozygous genotype TNFB1 and TNFB2 has a higher risk of developing post operative infection. In general, TNFB2 homozygous genotype is significantly associated with development of postoperative sepsis. This suggests a genetic determination of the individual inflammatory response, which significantly influences susceptibility to postoperative infection in joint care surgeries
Disclosure of Interest None Declared
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