Heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia.
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.
Waterer
Grant W
GW
Department of Medicine, University of Western Australia. waterer@cyllene.uwa.edu.au
ElBahlawan
Lama
L
Quasney
Michael W
MW
Zhang
Qing
Q
Kessler
Lori A
LA
Wunderink
Richard G
RG
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*
D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha