A tumor necrosis factor gene polymorphism influences the inflammatory response after cardiac operation

The genetic background may influence cytokine release evoked by cardiac operation. Thus we determined the allele frequency and genotype distribution of a bi-allelic tumor necrosis factor (TNF) gene polymorphism and TNF-alpha concentrations in patients undergoing cardiac operations with and without cardiopulmonary bypass (CPB).

The TNF NcoI gene polymorphism was identified by polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. Reading the size of the resulting DNA bands from the agarose gel defined the genotype as homozygous or heterozygous for the two alleles TNFB1 and TNFB2. Blood samples to determine TNF-alpha plasma levels were drawn from the patients before induction of general anesthesia after termination of CPB or after finishing coronary revascularization on the beating heart in non-CPB patients and 12 hours postoperatively.

The genotype distribution and allele frequencies in 47 patients undergoing cardiac operation with CPB were comparable with those found in 36 patients undergoing cardiac operation without CPB. The TNF-alpha plasma levels over time were comparable in patients with and without CPB. However, patients homozygous for the TNF-B2 allele had significantly higher TNF-alpha plasma levels after termination of the CPB (40.2 +/- 3.5 pg/mL; mean +/- standard error of the mean; n = 28) compared with non-CPB patients (29.8 +/- 2.5 pg/mL; mean +/- standard error of the mean; n = 15) (p < 0.05).

Patients homozygous for the TNF-B2 allele showed significantly higher TNF-alpha plasma levels after termination of CPB compared with non-CPB patients. Therefore preoperative TNF genotyping may be useful as patients with genetically determined increased proinflammatory cytokine expression with multiple comorbidities may in particular benefit from avoiding the use of CPB.