Tumor necrosis factor alpha influences the inflammatory response after coronary surgery

Background. A systemic inflammatory response is not uncommonly observed after coronary revascularization. Tumor necrosis factor alpha is one of a number of modulators of this response. A functional polymorphism within the TNF alpha gene at position G-308A has been associated with increased TNF alpha levels. The relationship between predicted TNF alpha genotype and circulating TNF alpha levels in patients undergoing coronary revascularization surgery has yet to be defined. We examined the relationship between TNF alpha G-308A polymorphism, TNF alpha postoperative levels, and clinical outcome after coronary revascularization surgery. Methods. We obtained DNA from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for TNF alpha G-308A polymorphism using sequence specific primer-polymerase chain reaction (SSP-PCR). Tumor necrosis factor alpha levels were measured on serum samples taken 3 hours postoperatively using enzyme-linked immunosorbent assay (ELISA). Results. The prevalence of AA, AG, and GG TNF alpha-308 genotype was 12%, 40%, and 48%, respectively. Patients homozygous for A had higher circulating levels of TNF alpha (p = 0.009). Higher levels of TNF alpha were significantly associated with prolonged intensive care unit stay (p = 0.008), increase usage of an inotropic agent (p = 0.024), increased mortality risk (p = 0.018), and diabetes (p = 0.019). These remained statistically significant after risk stratification. Conclusions. Patients of the AA-308 TNF alpha genotype showed significantly higher TNF alpha plasma levels. Higher plasma levels of TNF alpha were associated with less favorable outcome after coronary revascularization surgery. It may prove useful to utilize TNF alpha serum levels as a marker for identifying high-risk patients in the future.