To our knowledge, this was the first relatively large-scale study investigating associations of genetic variants within TNF, LTA, TNFRSF1A and TNFRSF1B with severe sepsis in Chinese Han population. Our results provided evidence that rs1800629, a functional SNP in the promoter region of TNF, was significantly associated with susceptibility to severe sepsis in Chinese Han population. The association between rs1800629 and severe sepsis risk may be explained by its influence on the expression of TNF-a. In this study, we found that the risk allele (rs1800629A) is associated with increased TNF-a production in PBMCs from healthy subjects after stimulation with LPS. Moreover, we found that TNF-a serum levels in severe sepsis patients with AA+AG genotypes for rs1800629 were significantly higher than those in the individuals with GG genotype. Previous studies also showed that rs1800629A allele was associated with a six fold higher expression of both basal and induced TNF mRNA [39, 40] . Menges et al. found that the plasma TNF-a concentrations in patients with sepsis secondary to severe traumatic injury were significantly elevated in rs1800629A carriers on the first day after admission and for the following 14 days [41] . As TNF-a plays a pivotal role in the pathogenesis of severe sepsis in response to infection, it is reasonable to assume that patients with rs1800629A allele might produce a higher amount of TNF-a, and therefore become more susceptible to severe sepsis. In contrast to the TNF 2308G/A polymorphism, the LTA +252A/G was not associated with the development of severe sepsis in our study. Our data showed that 2308G/A of TNF and +252A/G of LTA were in weak linkage disequilibrium (LD) (D9 = 0.118) in Chinese Han population. The LD pattern is quite dissimilar to Caucasian population, which might result from the racial difference [24] .