Analysis of two human leukocyte antigen-linked polymorphic heat shock protein 70 genes in patients with severe sepsis

Objective: To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outco me of severe sepsis. Furthermore, we investigated a possible linkage betwee n HSP70 gene polymorphisms and the previously reported and mortality-relate d tumor necrosis factor-beta (TNF-beta) Ncol gene polymorphism. Design:Consecutive entry study of patients with severe sepsis. Setting: Surgical intensive care unit in a university hospital. Patients: Eighty-seven patients with a diagnosis of severe sepsis. Interven tions: None. Measurements and Main Results:We studied two bi-allelic polymorphisms withi n the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta Ncol polymorphisms were identified by mean s of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype a nd allelic frequencies were observed for both HSP70 gene polymorphisms betw een the 87 patients and the 110 healthy Caucasians serving as the control g roup. In addition, no differences in genotype and allelic frequencies betwe en surviving and nonsurviving patients were detected. The allelic frequenci es in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the H SP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis. Conclusions:Our data show that the bi-allelic Ncol and Pstl polymorphisms w ithin the HSP70-HOM and HSP70-2 locus, respectively, are associated with ne ither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and morta lity-related homozygous genotype, TNFB2/82, in patients suffering from seve re sepsis.