Influence of the TNF-α and TNF-β polymorphisms upon infectious risk and outcome in surgical intensive care patients

Jacqueline E. Calvano, John Y Um, Doreen M. Agnese, Sae J. Hahm, Ashwini Kumar, Susette M. Coyle, Steve E. Calvano, Stephen F. Lowry

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Tumor necrosis factor-alpha (TNF-α) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-α and TNF-β genes (TNF2 and LTA+250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-α and-β genes are associated with an increased risk of infection in an at-risk surgical intensive care population. Materials and Methods: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing. Results: Eighty-six percent of the patients were TNF1 homozygotes (G:G at-308 of the TNF-α promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-β, whereas the homozygous A:A was present in 45.4% of the patients. Conclusion: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalSurgical Infections
Volume4
Issue number2
DOIs
StatePublished - Jan 1 2003

Fingerprint

Critical Care
Tumor Necrosis Factor-alpha
Septic Shock
Alleles
Sepsis
Genes
Systemic Inflammatory Response Syndrome
Mortality
Homozygote
Chloroform
Phenol
Infection
Genetic Promoter Regions
Critical Illness
Electrophoresis
Digestion
Gels
Genotype
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Surgery
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Influence of the TNF-α and TNF-β polymorphisms upon infectious risk and outcome in surgical intensive care patients. / Calvano, Jacqueline E.; Um, John Y; Agnese, Doreen M.; Hahm, Sae J.; Kumar, Ashwini; Coyle, Susette M.; Calvano, Steve E.; Lowry, Stephen F.

In: Surgical Infections, Vol. 4, No. 2, 01.01.2003, p. 163-169.

Research output: Contribution to journalArticle

Calvano, Jacqueline E. ; Um, John Y ; Agnese, Doreen M. ; Hahm, Sae J. ; Kumar, Ashwini ; Coyle, Susette M. ; Calvano, Steve E. ; Lowry, Stephen F. / Influence of the TNF-α and TNF-β polymorphisms upon infectious risk and outcome in surgical intensive care patients. In: Surgical Infections. 2003 ; Vol. 4, No. 2. pp. 163-169.
@article{d1030b0eefd04f5d9774d2ce0d656175,
title = "Influence of the TNF-α and TNF-β polymorphisms upon infectious risk and outcome in surgical intensive care patients",
abstract = "Background: Tumor necrosis factor-alpha (TNF-α) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-α and TNF-β genes (TNF2 and LTA+250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-α and-β genes are associated with an increased risk of infection in an at-risk surgical intensive care population. Materials and Methods: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing. Results: Eighty-six percent of the patients were TNF1 homozygotes (G:G at-308 of the TNF-α promoter region), whereas 9{\%} of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6{\%} of the patients exhibited the G:G alleles for TNF-β, whereas the homozygous A:A was present in 45.4{\%} of the patients. Conclusion: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.",
author = "Calvano, {Jacqueline E.} and Um, {John Y} and Agnese, {Doreen M.} and Hahm, {Sae J.} and Ashwini Kumar and Coyle, {Susette M.} and Calvano, {Steve E.} and Lowry, {Stephen F.}",
year = "2003",
month = "1",
day = "1",
doi = "10.1089/109629603766956951",
language = "English (US)",
volume = "4",
pages = "163--169",
journal = "Surgical Infections",
issn = "1096-2964",
publisher = "Mary Ann Liebert Inc.",
number = "2",

}

TY - JOUR

T1 - Influence of the TNF-α and TNF-β polymorphisms upon infectious risk and outcome in surgical intensive care patients

AU - Calvano, Jacqueline E.

AU - Um, John Y

AU - Agnese, Doreen M.

AU - Hahm, Sae J.

AU - Kumar, Ashwini

AU - Coyle, Susette M.

AU - Calvano, Steve E.

AU - Lowry, Stephen F.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Background: Tumor necrosis factor-alpha (TNF-α) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-α and TNF-β genes (TNF2 and LTA+250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-α and-β genes are associated with an increased risk of infection in an at-risk surgical intensive care population. Materials and Methods: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing. Results: Eighty-six percent of the patients were TNF1 homozygotes (G:G at-308 of the TNF-α promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-β, whereas the homozygous A:A was present in 45.4% of the patients. Conclusion: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.

AB - Background: Tumor necrosis factor-alpha (TNF-α) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-α and TNF-β genes (TNF2 and LTA+250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-α and-β genes are associated with an increased risk of infection in an at-risk surgical intensive care population. Materials and Methods: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing. Results: Eighty-six percent of the patients were TNF1 homozygotes (G:G at-308 of the TNF-α promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-β, whereas the homozygous A:A was present in 45.4% of the patients. Conclusion: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.

UR - http://www.scopus.com/inward/record.url?scp=0042921428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042921428&partnerID=8YFLogxK

U2 - 10.1089/109629603766956951

DO - 10.1089/109629603766956951

M3 - Article

VL - 4

SP - 163

EP - 169

JO - Surgical Infections

JF - Surgical Infections

SN - 1096-2964

IS - 2

ER -