Influence of cytokine genomic polymorphisms on the susceptibility and outcome of severe sepsis

Objective To investigate the correlations between the polymorphisms of TNFα,TNFβ,IL-1β and IL-1ra gene and the susceptibility or outcome of severe sepsis.Methods A prospective,consecutive entry study was made among 59 patients with severe sepsis admitted in ICU,Nanjing ZhongDa Hospital between 2001 and 2002.The genomic DNA of peripheral blood nucleated was extracted.The region containing the polymorphism sites of TNFα,TNFβ and IL-1β gene was amplified by polymerase chain reaction (PCR) and restrictive fragment length polymorphism (RFLP).The polymorphic region within intron 2 of the IL-1ra gene was amplified by PCR.Results The frequency of allele TNF 2 of TNFα was 15.3% in the 59 patients with severe sepsis,higher than that in normal controls [7.5%(P=0.018)],with an odds ratio of 2.232.The frequencies of genotype TNF 2/TNF 2 in the 59 patients with severe sepsis and normal controls were 10.2% and 1.5% respectively (P=0.020),with an odds ratio of 7.472.The polymorphisms of TNFβ,IL-1β and IL-1ra did not differ between the patients with severe sepsis and normal controls.The frequency of allele TNB 2 of TNFβ was 73.1% in the nonsurvivors,higher than in the survivors 31.5%(P=0.004),with an odds ratio of 5.897.The frequency of TNB 2/TNB 2 was increased in the nonsurvivors compared with survivors,with an odds ratio of 6.500(P=0.004).The allele frequency and genotype distribution of TNFα,IL-1β and IL-1ra did not differ between the surviors and nonsurviors.Conclusion The allele TNF 2 of TNFα NcoI polymorphism may contribute to susceptibility to severe sepsis.The allele TNFB 2 of TNFβ NcoI polymorphism may be a genomic marker indicating poor prognosis.