Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations

G. W. Waterer, M. W. Quasney, R. M. Cantor, R. G. Wunderink*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Genetic factors are likely to contribute to the variable presentation of community-acquired pneumonia (CAP). The purpose of this prospective cohort study was to determine whether the LTα+250 (TNFβ3+250) and TNFα-308 gene polymorphisms are associated with different presentations of CAP. Septic shock (SS) was defined using American College of Chest Physicians/Society of Critical Care Medicine (ACCP-SCCM) criteria. Type I respiratory failure (T1RF) was defined as an O2 saturation on room air of < 90% with a normal Pco2. A total of 280 patients were genotyped; 31 had SS, 80 had T1RF. Genotype proportions are given in the order of AA/GA/ GG. The proportion of patients in each genotype developing SS was as follows: LTα+250 0.19/0.07/0.09 (p = 0.01 AA versus nonAA); TNFα-308 0.16/0.06/0.12 (p = NS). Carrying at least one AA (tumor necrosis factor [TNF] high secretor) genotype had an 18.0% risk of SS versus 6.8% (p = 0.006). GG homozygotes (TNF low secretors) at both loci had only a 2.9% risk of SS. Septic shock was associated with the LTα+250:TNFα-308 A:G haplotype but not the A:A haplotype, suggesting that LTα+250 is a marker, rather than a causative polymorphism. Carriage of the G:G haplotype had a significant protective effect against the development of septic shock (p = 0.011). T1RF was not associated with LTα+250 AA genotype. In the absence of septic shock, there was a significant trend to greater T1RF in patients with LTα+250 GG (TNFα hyposecretor) genotype (p = 0.03). Our finding of different genotype associations for SS and T1RF has important implications for immunotherapy in both CAP and sepsis, as well as for the definition of the systemic inflammatory response syndrome (SIRS).

Original languageEnglish (US)
Pages (from-to)1599-1604
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number7
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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