Premium
Polymorphisms of the tumour necrosis factor‐α gene, coronary heart disease and obesity
Author(s) -
Stefan Herrmann,
Sylvain Ricard,
Viviane Nicaud,
Christine Mallet,
Dominique Arveiler,
Alun Evans,
JeanBernard Ruidavets,
Gérald Luc,
L. Bara,
HenriJoseph Parra,
Odette Poirier,
François Cambien
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00244.x
Subject(s) - genotype , allele , medicine , genetics , population , obesity , biology , immunology , endocrinology , gene , environmental health
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; 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‐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.