title: Heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia.
abstract: OBJECTIVE
  Heat shock protein (HSP)70-2 is an important immunomodulatory protein induced in response to inflammatory stimuli. We assessed whether HSP70-2+1267 genotype influenced the risk of septic shock in a prospective cohort study of community-acquired pneumonia and whether HSP70-2+1267 genotype is a better predictor of septic shock than the genotype at lymphotoxin-alpha +250.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  A large, nonprofit, private hospital system in Memphis, TN.
  
  
  METHODS
  Adults admitted with community-acquired pneumonia between 1998 and 2001. Septic shock was defined according to consensus criteria (American College of Chest Physicians/Society of Critical Care Medicine, 1992).
  
  
  METHODS
  Blood sampling.
  
  
  RESULTS
  A total of 343 subjects were enrolled; 30 had septic shock. HSP70-2+1267 and lymphotoxin-alpha +250 genotype was determined using polymerase chain reaction and restriction enzyme digestion. HSP70-2+1267 AA genotype was the strongest predictor of septic shock (p =.0005; relative risk, 3.5). Lymphotoxin-alpha +250 AA genotype was also associated with an increased risk of septic shock (p =.002; relative risk, 2.7). Logistic regression analysis found only age (p =.04) and HSP70-2+1267 genotype (p =.006) were predictors of septic shock. The greatest risk of septic shock was associated with carriage of the HSP70-2+1267 A/lymphotoxin-alpha +250 A haplotype (p <.0001).
  
  
  CONCLUSIONS
  HSP70-2+1267 genotype is a stronger predictor of septic shock in patients with community-acquired pneumonia than lymphotoxin-alpha +250 genotype.
authors.affiliation: Department of Medicine, University of Western Australia. waterer@cyllene.uwa.edu.au
authors.forename: Grant W
authors.initials: GW
authors.lastname: Waterer
authors.forename: Lama
authors.initials: L
authors.lastname: ElBahlawan
authors.forename: Michael W
authors.initials: MW
authors.lastname: Quasney
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kessler
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017714:Community-Acquired Infections / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000150:complications*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012772:Shock, Septic / Q000235:genetics* / Q000401:mortality; D013714:Tennessee / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha