title: Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity.
abstract: BACKGROUND
  Tumour necrosis factor-alpha (TNF-alpha) is a cytokine that has multiple functions. Through its effects on lipid metabolism, coagulation, insulin resistance and endothelial function, TNF-alpha could be involved in cardiovascular pathophysiology. Given this possibility, we hypothesized that polymorphisms of the TNF-alpha gene might be associated with a predisposition to coronary heart disease (CHD).
  
  
  METHODS
  The entire coding region and 1053 bp upstream of the transcription start site of the TNF-alpha gene were screened for polymorphisms using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing. Five polymorphisms were identified: four were located in the upstream region at positions -857, -851, -308, -238 from the first transcribed nucleotide and one was found in a non-translated region at position +691. Six-hundred and forty-one patients with myocardial infarction (MI) and 710 control subjects from the ECTIM Study were genotyped.
  
  
  RESULTS
  The genotype frequencies were similar in cases and control subjects in the high-risk population of Belfast and in France; however, the TNF-alpha/-308A allele was more frequent in Belfast than in France (0.242 vs. 0.157; P < 0.0001), and carriers of this allele were more frequently obese than non-carriers [1.52 (1.15-1.99), P < 0.004]. No associations were found for the other polymorphisms.
  
  
  CONCLUSIONS
  These results suggest that polymorphisms of the TNF-alpha gene are unlikely to contribute to CHD risk in an important way, but the TNF-alpha/-308 polymorphism should be investigated further in relation to obesity.
authors.affiliation: INSERM SC7, Paris, France.
authors.forename: S M
authors.initials: SM
authors.lastname: Herrmann
authors.forename: S
authors.initials: S
authors.lastname: Ricard
authors.forename: V
authors.initials: V
authors.lastname: Nicaud
authors.forename: C
authors.initials: C
authors.lastname: Mallet
authors.forename: D
authors.initials: D
authors.lastname: Arveiler
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: J B
authors.initials: JB
authors.lastname: Ruidavets
authors.forename: G
authors.initials: G
authors.lastname: Luc
authors.forename: L
authors.initials: L
authors.lastname: Bara
authors.forename: H J
authors.initials: HJ
authors.lastname: Parra
authors.forename: O
authors.initials: O
authors.lastname: Poirier
authors.forename: F
authors.initials: F
authors.lastname: Cambien
mesh_terms: D000328:Adult; D017023:Coronary Angiography; D003327:Coronary Disease / Q000235:genetics*; D005602:France; D015803:HLA-DR3 Antigen / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D009660:Northern Ireland; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha