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Genetic variation in heat shock protein 70 is associated with septic shock: narrowing the association to a specific haplotype
Author(s) -
Kee C.,
Cheong K. Y.,
Pham K.,
Waterer G. W.,
Temple S. E. L.
Publication year - 2008
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2008.00812.x
Subject(s) - haplotype , heat shock protein , hsp70 , biology , septic shock , tumor necrosis factor alpha , gene , peripheral blood mononuclear cell , shock (circulatory) , immunology , genotype , microbiology and biotechnology , genetics , sepsis , medicine , in vitro
Summary Heat shock protein 70 (HSP70) plays a major role in immune responses. Polymorphisms within the gene have been associated with development of septic shock. This study refines the region of the HSP70 gene associated with development of septic shock and confirms its functionality. Subjects ( n = 31) were grouped into one of three haplotypes based on their HSPA1B‐179C>T and HSPA1B1267A>G genotypes. Mononuclear cells from these subjects were stimulated with heat‐killed bacteria (10 7 colony‐forming units/mL Escherichia coli or Streptococcus pneumoniae ) for 8 and 21 h. HSP70 and tumour necrosis factor (TNF) mRNA and protein levels were measured by reverse transcriptase‐polymerase chain reaction and ELISA, respectively. The HSPA1B‐179*C:1267*A haplotype was associated with significantly lower levels of HSPA1B mRNA and protein and higher production of TNF mRNA and protein compared to the other haplotypes. Induction of HSP70 was TNF independent. These results suggest that the HSPA1B‐179C>T:1267A>G haplotype is functional and may explain the association of the HSP70 gene with development of septic shock.