Tumor necrosis factor gene polymorphisms and inflammatory response in coronary artery bypass grafting patients

Abstract

Background—Tumor necrosis factor‐α (TNF‐α), a key factor in the inflammatory cascade, has been implicated in coronary artery disease. Two biallelic polymorphisms in the TNF gene locus (TNFA at position −308 and TNFB at +252) may influence TNF‐α production. Individuals with the rare TNFA2 allele or TNFB2 homozygosity have augmented TNF‐α production. We investigated the genotypes associated with increased TNF‐α production in coronary artery bypass grafting (CABG) patients and if these genotypes influence the magnitude of the postoperative inflammatory response.Methods—TNF gene polymorphisms were analyzed by multiplex fluorescent solid‐phase minisequencing in 86 CABG patients. Plasma concentrations of TNF‐α, IL‐6 and C3a and C‐reactive protein (CRP) were analyzed before and after surgery in 45 of the patients and compared with genetically high and low TNF‐α producers.Results—Thirty percent of the patients carried the TNFA2 allele and 45% were TNFB2 homozygous. The allelic frequencies were TNFA1/TNFA2 = 0.84/0.16 and TNFB1/TNFB2 = 0.32/0.68. Pre‐ and postoperative levels of TNF‐α, IL‐6, C3a and CRP did not differ significantly between genetically high and low TNF‐α producers.Conclusions—The frequency of high TNF‐α producing genotypes in a CABG population was comparable to that previously reported from normal populations. Furthermore, we found no evidence that the investigated TNF‐α gene polymorphisms influence postoperative inflammatory response after uncomplicated coronary surgery.