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Keywords:

  • Gene polymorphism;
  • myocardial infarction;
  • obesity;
  • plasma lipoproteins;
  • TNF-α

Background

Tumour necrosis factor-α (TNF-α) is a cytokine that has multiple functions. Through its effects on lipid metabolism, coagulation, insulin resistance and endothelial function, TNF-α could be involved in cardiovascular pathophysiology. Given this possibility, we hypothesized that polymorphisms of the TNF-α 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-α 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-α/−308A allele was more frequent in Belfast than in France (0.242 vs. 0.157; < 0.0001), and carriers of this allele were more frequently obese than non-carriers [1.52 (1.15–1.99), < 0.004]. No associations were found for the other polymorphisms.

Conclusions

These results suggest that polymorphisms of the TNF-α gene are unlikely to contribute to CHD risk in an important way, but the TNF-α/−308 polymorphism should be investigated further in relation to obesity.