Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury

Crit Care Med. 2003 Jan;31(1):73-9. doi: 10.1097/00003246-200301000-00011.

Abstract

Objective: To examine the influence of genetic variations in heat shock proteins on trauma outcome.

Design: Prospective, noninterventional, single-center study.

Setting: Level I trauma center.

Subjects: Eighty consecutive severe multiple trauma patients.

Interventions: None.

Measurements and main results: Plasma concentrations of interleukin-6 and tumor necrosis factor-alpha were measured over a 5-day course by chemiluminescence-immunoassay. The genotypes of the polymorphisms HSPA1B (HSP70-2) G1538A and HSPA1L (HSP70-Hom) C2437T were determined by polymerase chain reaction and restriction cleavage with PstlI or NcoI, respectively. Allele frequency of the HSPA1B 1538 G allele was 0.569, and that of the HSPA1L 2437 T allele was 0.821. Interleukin-6 concentrations rapidly increased and dropped to almost normal after 5 days, whereas tumor necrosis factor-alpha concentrations increased until day 5. Patients carrying the genotypes HSPA1B AG or HSPA1L CT had significantly higher plasma concentrations of tumor necrosis factor-alpha and interleukin-6 compared with those with genotype GG or TT. Presence of the HSPA1L genotype CT also was a significant risk factor to develop liver failure (odds ratio, 4.6; 95% confidence interval, 1.5-14.1) and to acquire at least one complication severe enough to score three points according to the Denver multiple organ failure score (odds ratio, 3.0; 95% confidence interval, 1.1-9.2).

Conclusion: The data indicate that genetic variations of the heat shock proteins HSPA1B and HSPA1L may contribute to clinical outcome after severe injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Female
  • Gene Frequency
  • Genetic Markers*
  • Germany / epidemiology
  • Heat-Shock Proteins / genetics*
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Multiple Organ Failure / epidemiology
  • Multiple Organ Failure / genetics
  • Multiple Trauma / genetics*
  • Multiple Trauma / immunology
  • Multiple Trauma / mortality
  • Polymorphism, Genetic*
  • Prospective Studies
  • Statistics, Nonparametric
  • Survival Rate
  • Systemic Inflammatory Response Syndrome / epidemiology
  • Systemic Inflammatory Response Syndrome / genetics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Genetic Markers
  • Heat-Shock Proteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha