Objective: To investigate the association of Single nucleotide polymorphism (SNPs) tumor necrosis factor (TNF) and CD14 promoter with the systematic inflammatory response syndromec (SIRS) and sepsis in surgical patients.
Methods: The DNA and RNA sample of PBMC from 113 patients, 40 of them being complicated with sepsis, and 100 healthy volunteers were extracted. The SNP genotypes of TNF-alpha -308 G/A, -863 C/A, CD14-159C/T and TNFB1/B2 were examined by restriction fragment length polymorphism PCR (PCR-RFLP). The expressions of TNF-alpha mRNA of PBMC in parts of the patients who have at least one genotype of SNP were detected by RT-PCR. The risks for sepsis associated with polymorphisms in the TNF-alpha or CD14 promoter were determined by multivariate analysis.
Results: The rates of TNF2, -863A, CD14-159T alleles were 15%, 32.5%, and 40% respectively in patients with sepsis, significantly higher than those in the patients with SIRS (8.9%, 22%, and 23.3%), and those in the healthy volunteers (5%, 16% and 26%). The expression of TNF-alpha mRNA was much higher in those patients with at least one kind of SNP than those without SNP.
Conclusion: The A-allele at the -308 and -863 position in the TNF-alpha promoter and the T-allele at the -159 position in the CD14 promoter increase the risk for sepsis. The effect of SNP genotypes on TNF-alpha expression can modulate inflammatory response.