Angiotensin-Converting Enzyme Gene Polymorphism Is Associated With Myocardial Infarction but Not With Development of Coronary Stenosis
| Autor: | Jeffrey L. Anderson, E. H. Ludwig, Jean-Marc Lalouel, Hiram W. Marshall, Patrice Showers Corneli, R. H. Ward |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Genotype Myocardial Infarction Coronary Disease Peptidyl-Dipeptidase A Coronary Angiography Polymerase Chain Reaction Body Mass Index law.invention Renin-Angiotensin System Coronary artery disease Pathogenesis Gene Frequency Risk Factors law Physiology (medical) Internal medicine Renin–angiotensin system medicine Humans Myocardial infarction Polymerase chain reaction Aged Polymorphism Genetic biology business.industry Angiotensin-converting enzyme Middle Aged medicine.disease Endocrinology DNA Transposable Elements biology.protein Cardiology Female Gene polymorphism Cardiology and Cardiovascular Medicine business Gene Deletion |
| Zdroj: | Circulation. 91:2120-2124 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.91.8.2120 |
| Popis: | Background Although both genetic and nongenetic factors contribute to the pathogenesis of coronary artery disease, the identification of specific genetic lesions has lagged behind the identification of critical environmental risk factors. A reported association between myocardial infarction (MI) and the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in European men suggests a critical role for this genomic region. However, the generality of this association remains to be determined. It also is not clear at what stage in disease progression the association with the ACE I/D polymorphism becomes important. Methods and Results We evaluated the ACE I/D polymorphism in patients who had undergone coronary angiography (402 men and 295 women) and in 203 representative control subjects. After polymerase chain reaction amplification, genotypes were determined by agarose gel sizing and by hybridization with allele-specific oligonucleotides. After patients were categorized by the degree of coronary artery stenosis and the occurrence of an MI, the distribution of ACE I/D genotypes was evaluated by log linear analysis. Patients were genetically representative of the regional population, and patients with >60% stenosis of their coronary arteries had the same distribution of ACE I/D genotypes as did patients with D allele in all patients (odds ratio [OR], 1.59; P =.002) and in men alone (OR, 1.63; P =.006). The lack of significance in women (OR, 1.40; P =.263) is probably due to the fact that only 36 women in the present study had experienced an MI. Furthermore, the association between MI and the ACE I/D polymorphism was independent of blood pressure, smoking habits, and body mass index. Conclusions Segregation of the ACE I/D polymorphism is a pervasive genetic risk factor for MI in whites but has no evident effect on the events leading to stenosis of the coronary arteries. This suggests that risk of MI is influenced by two independent processes—atherogenesis that leads to coronary stenosis followed by conversion to MI. The renin-angiotensin system appears to confer significant risk of infarction by influencing the conversion to MI but has no apparent effect on the development of atherostenosis. |
| Databáze: | OpenAIRE |
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