title: Tumor necrosis factor alpha influences the inflammatory response after coronary surgery.
abstract: BACKGROUND
  A systemic inflammatory response is not uncommonly observed after coronary revascularization. Tumor necrosis factor alpha is one of a number of modulators of this response. A functional polymorphism within the TNFalpha gene at position G-308A has been associated with increased TNFalpha levels. The relationship between predicted TNFalpha genotype and circulating TNFalpha levels in patients undergoing coronary revascularization surgery has yet to be defined. We examined the relationship between TNFalpha G-308A polymorphism, TNFalpha postoperative levels, and clinical outcome after coronary revascularization surgery.
  
  
  METHODS
  We obtained DNA from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for TNFalpha G-308A polymorphism using sequence specific primer-polymerase chain reaction (SSP-PCR). Tumor necrosis factor alpha levels were measured on serum samples taken 3 hours postoperatively using enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The prevalence of AA, AG, and GG TNFalpha-308 genotype was 12%, 40%, and 48%, respectively. Patients homozygous for A had higher circulating levels of TNFalpha (p = 0.009). Higher levels of TNFalpha were significantly associated with prolonged intensive care unit stay (p = 0.008), increase usage of an inotropic agent (p = 0.024), increased mortality risk (p = 0.018), and diabetes (p = 0.019). These remained statistically significant after risk stratification.
  
  
  CONCLUSIONS
  Patients of the AA-308 TNFalpha genotype showed significantly higher TNFalpha plasma levels. Higher plasma levels of TNFalpha were associated with less favorable outcome after coronary revascularization surgery. It may prove useful to utilize TNFalpha serum levels as a marker for identifying high-risk patients in the future.
authors.affiliation: Department of Cardiothoracic Surgery, South Manchester University Hospitals NHS Trust, Wythenshawe Hospital, United Kingdom. mbittar@doctors.org.uk
authors.forename: Mohamad N
authors.initials: MN
authors.lastname: Bittar
authors.forename: John A
authors.initials: JA
authors.lastname: Carey
authors.forename: James B
authors.initials: JB
authors.lastname: Barnard
authors.forename: Vera
authors.initials: V
authors.lastname: Pravica
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Deiraniya
authors.forename: Nizar
authors.initials: N
authors.lastname: Yonan
authors.forename: Ian V
authors.initials: IV
authors.lastname: Hutchinson
mesh_terms: D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004252:DNA Mutational Analysis; D017558:Elective Surgical Procedures; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000209:etiology / Q000503:physiopathology*; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha