Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity

Eur J Clin Invest. 1998 Jan;28(1):59-66. doi: 10.1046/j.1365-2362.1998.00244.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coronary Angiography
  • Coronary Disease / genetics*
  • France
  • HLA-DR3 Antigen / genetics
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / genetics
  • Northern Ireland
  • Obesity / genetics*
  • Polymorphism, Genetic / genetics*
  • Tumor Necrosis Factor-alpha / genetics*


  • HLA-DR3 Antigen
  • Tumor Necrosis Factor-alpha