title: Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury.
abstract: OBJECTIVE
  To examine the influence of genetic variations in heat shock proteins on trauma outcome.
  
  
  METHODS
  Prospective, noninterventional, single-center study.
  
  
  METHODS
  Level I trauma center.
  
  
  METHODS
  Eighty consecutive severe multiple trauma patients.
  
  
  METHODS
  None.
  
  
  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).
  
  
  CONCLUSIONS
  The data indicate that genetic variations of the heat shock proteins HSPA1B and HSPA1L may contribute to clinical outcome after severe injury.
authors.affiliation: Department of Trauma Surgery, Ernst Moritz Arndt University of Greifswald and Unfallkrankenhaus Berlin, Germany.
authors.forename: Ove
authors.initials: O
authors.lastname: Schröder
authors.forename: Klaus-Martin
authors.initials: KM
authors.lastname: Schulte
authors.forename: Peter
authors.initials: P
authors.lastname: Ostermann
authors.forename: Hans-Dietrich
authors.initials: HD
authors.lastname: Röher
authors.forename: Axel
authors.initials: A
authors.lastname: Ekkernkamp
authors.forename: Reinhold Alexander
authors.initials: RA
authors.lastname: Laun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005858:Germany / Q000453:epidemiology; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology / Q000235:genetics; D009104:Multiple Trauma / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology / Q000235:genetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D005819:Genetic Markers; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha