Polymorphisms of the tumour necrosis factor-α gene, coronary heart disease and obesity
| Autor: | Alun Evans, F. Cambien, Dominique Arveiler, Viviane Nicaud, Christine Mallet, Odette Poirier, H.-J. Parra, Sylvain Ricard, L. Bara, Stefan-Martin Herrmann, G. Luc, Jean-Bernard Ruidavets |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
education.field_of_study business.industry Clinical Biochemistry Population General Medicine medicine.disease Biochemistry Genotype frequency Insulin resistance Endocrinology Internal medicine Medicine Coding region Myocardial infarction Gene polymorphism Allele business education Gene |
| Zdroj: | European Journal of Clinical Investigation. 28:59-66 |
| ISSN: | 0014-2972 |
| DOI: | 10.1046/j.1365-2362.1998.00244.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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