Tumor necrosis factor gene polymorphisms and inflammatory response in coronary artery bypass grafting patients.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha), 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-alpha production. Individuals with the rare TNFA2 allele or TNFB2 homozygosity have augmented TNF-alpha production. We investigated the genotypes associated with increased TNF-alpha 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-alpha, 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-alpha 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-alpha, IL-6, C3a and CRP did not differ significantly between genetically high and low TNF-alpha producers.


CONCLUSIONS
The frequency of high TNF-alpha producing genotypes in a CABG population was comparable to that previously reported from normal populations. Furthermore, we found no evidence that the investigated TNF-alpha gene polymorphisms influence postoperative inflammatory response after uncomplicated coronary surgery.
Westerberg
Martin
M
Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. martin.westerberg@hjl.gu
Bengtsson
Anders
A
Ricksten
Anne
A
Jeppsson
Anders
A
D000368:Aged; D000483:Alleles; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000235:genetics* / Q000601:surgery; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha