Polymorphisms of the tumour necrosis factor-α gene, coronary heart disease and obesity
Version of Record online: 25 DEC 2001
Blackwell Science Ltd, Oxford
European Journal of Clinical Investigation
Volume 28, Issue 1, pages 59–66, January 1998
How to Cite
Herrmann, Ricard, Nicaud, Mallet, Arveiler, Evans, Ruidavets, Luc, Bara , Parra, Poirier and Cambien (1998), Polymorphisms of the tumour necrosis factor-α gene, coronary heart disease and obesity. European Journal of Clinical Investigation, 28: 59–66. doi: 10.1046/j.1365-2362.1998.00244.x
- Issue online: 25 DEC 2001
- Version of Record online: 25 DEC 2001
- Cited By
- Gene polymorphism;
- myocardial infarction;
- plasma lipoproteins;
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).
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.
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; 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.
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.