Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphisms : association with early coronary disease

• Published in: Cardiovascular research Vol. 40; no. 2; pp. 375 - 379
• Main Authors: ALVAREZ, R, REGUERO, J. R, BATALLA, A, IGLESIAS-CUBERO, G, CORTINA, A, ALVAREZ, V, COTO, E
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-1998
• Subjects: Adult; Biological and medical sciences; Cardiology. Vascular system; Case-Control Studies; Coronary Disease - genetics; Coronary heart disease; Genotype; Heart; Humans; Male; Medical sciences; Middle Aged; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin - genetics; Risk; Human; Enzyme; Cardiovascular disease; Coronary heart disease; Genetic determinism; Peptidases; Peptidyl-dipeptidase A; Risk factor; Hydrolases; Peptidyl-dipeptidases; Early; Angiotensin II; Polymorphism; Biological receptor
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(98)00179-5

To examine the association between coronary artery disease and polymorphisms at the angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) genes.
A total of 181 patients younger than 50 years and 240 controls from the same homogeneous Caucasian population (Asturias, Northern Spain) were genotyped (using polymerase chain reaction) for the ACE insertion/deletion (ACE-I/D) and the AT1R A/C transversion (AT1R-A/C) (3-untranslated region) polymorphisms.
The DD-genotype was at a non-significant higher frequency among patients (50%) than in controls (41%). No difference between the two groups was found for the AT1R-genotypes. Distribution of ACE-genotypes according to AT1R-genotypes showed a significant association between ACE-DD and AT1R-CC and early coronary disease. Among the CC patients 58% were DD, compared to 21% among the controls (p = 0.02; OR = 5.32, 95% CI = 1.45, 19.51). We determined the distribution of these genotypes among the hypertensive and non-hypertensive patients. Frequencies of ACE- or AT1R-genotypes did not differ between the two groups. However, we found an interaction between the DD- and CC-genotypes in the group of normotensives. Among the CC patients, 13% of the hypertensives and 75% of the normotensives were DD (p = 0.014).
Our results indicate a synergistic contribution of ACE and AT1R polymorphisms to the risk of coronary artery disease. This gene-gene interaction could have clinical implications. Approximately 2% of individuals in our population are CC + DD, and the genotyping of both polymorphisms could identify those with a high relative risk for coronary artery disease.