RESUMEN
The thymidine to cytosine transition at position 704 in exon 2 of the angiotensinogen gene leads to the amino acid substitution of threonine for methionine (T235 variant) and is responsible for elevated plasma levels of angiotensinogen. To examine the influence of T235 on the risk of coronary artery disease (CAD) we genotyped 184 CAD patients, 77 controls in whom CAD was excluded angiographically, and 155 healthy controls without signs of CAD by polymerase chain amplification and restriction enzyme digestion. Allele frequencies for A (wildtype) and a (mutant allele) in the total study population were 0.538 and 0.462, 0.536 and 0.464 in the healthy controls, and 0.481 and 0.519 in patients with excluded CAD, respectively. The allele frequencies and the genotype distribution in these groups did not show a significant difference. In conclusion, we did not observe an association between the T235 variant of the angiotensinogen gene and the risk of CAD.
Asunto(s)
Angiotensinógeno/genética , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética , Sustitución de Aminoácidos/genética , Angiografía Coronaria , ADN/química , ADN/genética , Electroforesis en Gel de Agar , Femenino , Genotipo , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
BACKGROUND: Elevated total plasma homocysteine levels are associated with an increased risk of coronary artery disease. Plasma homocysteine levels are influenced by nutritional and hereditary factors. A point mutation (cytosin to thymidine substitution; C677-->T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR), has been reported to render the enzyme thermolabile and has been associated with elevations in homocysteine levels in homozygous carriers (TT genotype). METHODS: To examine the hypothesis that the T allele (coding for the thermolabile defect of MTHFR) influences the risk of coronary artery disease, we genotyped 340 patients with coronary artery disease and 105 control subjects in whom coronary artery disease was excluded by coronary angiography. Furthermore, we studied the genotype frequency in 104 age- and sex-matched healthy persons as a control group without signs of atherosclerotic disease. RESULTS: Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 0.68 and 0.32 respectively in the healthy control subjects, 0.66 and 0.34 respectively in patients with angiographically excluded coronary artery disease and 0.69 and 0.31 respectively in coronary artery disease patients (P = NS). The allele frequencies of the total study population were 0.68 and 0.32. CONCLUSION: Our data show that homozygosity for the C677-->T mutation in this European population is not associated with increased risk of coronary artery disease. This finding suggests that the C677-->T mutation of the MTHFR gene does not represent a marker for increased cardiovascular risk.
