Contribution of genomic variations within human β-defensin 1 to incidence and outcome of severe sepsis

Sepsis, a systemic inflammatory response to infection, is a common clinical syndrome in the ICU. Human β-defensin 1 (DEFB1) is a multifunctional mediator in infection and inflammation, which has been largely explored in ex vivo studies. The lack of fully representative genetic animal models increases the importance of analyzing the impact of defensin gene polymorphisms on the courses of infectious and inflammatory diseases such as sepsis. This study was designed to investigate whether DEFB1 genomic variations are associated with incidence and outcome of severe sepsis. Six reported polymorphisms were detected in 211 patients with severe sepsis and 157 control individuals using diverse analytic methods. Linkage disequilibrium (LD), haplotype frequency, and statistical power for this association study were analyzed. The -44G-allele and -44G-allele carrying genotypes were significantly associated with incidence and outcome of severe sepsis. There was enough statistical power (1 – β > 0.8 at type I level of 0.05) to demonstrate a significant contribution of the -44G allele to severe sepsis. The -20G allele and GG genotype were associated with susceptibility to severe sepsis, while the -1816G-allele and -1816G-allele carrying genotypes influenced the outcome of severe sepsis. SNPs -20A/G, -44C/G and -52A/G were in strong LD. Haplotype -20A/-44C/-52G showed a protective role against severe sepsis, whereas haplotype -20G/-44G/-52G served as a risk factor for fatal outcome of severe sepsis. The present findings have important implications in the understanding of the role of DEFB1 in the pathophysiology of severe sepsis, and DEFB1 genomic variations may offer a new means of risk stratification for patients with severe sepsis.