Polymorphisms of heat shock protein-70 (HSPA1B and HSPA1L loci) do not influence infection or outcome risk in critically ill surgical patients.
Heat shock proteins (HSP) are induced in various stress conditions and have many cytoprotective effects, including formation of protein complexes for antigen presentation, stabilizing intracellular proteins, and facilitating protein folding. The HSP-70 gene exhibits polymorphisms at the HSPA1B and HSPA1L loci that reportedly influence cytokine levels and clinical outcomes in critically ill patients. These HSP variations also have been linked to TNF-beta polymorphisms associated with poor outcomes. This study further evaluated outcomes and risk of infection of HSP polymorphisms in critically ill patients. Seventy-six consecutive surgical intensive care unit uninfected patients with established systemic inflammatory response features were prospectively enrolled. Genomic DNA was isolated from whole blood samples and specific fragments, including the relevant polymorphic sites, were amplified by PCR, and restriction digestions were performed. Genotypes were determined by electrophoresis and all were confirmed by direct sequencing. Plasma cytokine levels for TNF-alpha were assayed in a subset of patients by enzyme-linked immunoabsorbent assay. None of the HSP alleles bore a significant relationship to nosocomial infection rates, organ specific dysfunctions, or mortality. No linkage of HSP genotype to common TNF-alpha or TNF-beta genotypes could be demonstrated, although the HSPA1L CT polymorphism was associated with higher levels of TNF-alpha compared with the TT genotype. These data suggest that polymorphisms of the HSPA1L or HSPA1B loci do not influence infection or other highly morbid outcomes in surgical intensive care unit patients.
Bowers
Daniel J
DJ
Division of Surgical Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08903, USA. bowersda@umdnj.edu
Calvano
Jacqueline E
JE
Alvarez
Sonia M
SM
Coyle
Susette M
SM
Macor
Marie A
MA
Kumar
Ashwini
A
Calvano
Steve E
SE
Lowry
Stephen F
SF
D000368:Aged; D003422:Critical Care; D016638:Critical Illness; D003428:Cross Infection / Q000209:etiology / Q000235:genetics*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011446:Prospective Studies; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha