Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity.
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.
Herrmann
S M
SM
INSERM SC7, Paris, France.
Ricard
S
S
Nicaud
V
V
Mallet
C
C
Arveiler
D
D
Evans
A
A
Ruidavets
J B
JB
Luc
G
G
Bara
L
L
Parra
H J
HJ
Poirier
O
O
Cambien
F
F
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*
D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha