Molecular Variant of Angiotensinogen Gene Is Associated With Coronary Atherosclerosis

Abstract

Background A positive association was previously reported between angiotensin-converting enzyme (ACE) gene polymorphism and several cardiovascular diseases, such as myocardial infarction, left ventricular hypertrophy, and restenosis after percutaneous transluminal coronary angioplasty. Plasma ACE activity and carotid-wall thickening measured by ultrasonography were related, and it was postulated that long-term exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall. In addition, angiotensinogen gene mutation was recently reported to be associated with essential hypertension and preeclampsia. There exists a possibility that the renin-angiotensin system plays an important role in the progress of cardiovascular diseases in humans. Therefore, we examined the association between the molecular variant of the angiotensinogen gene and coronary atherosclerosis. Methods and Results This study included 82 patients who had coronary atherosclerosis and 160 control subjects; all study participants were Japanese. All patients with coronary atherosclerosis had at least one coronary artery with >25% luminal diameter obstruction on average according to multiple coronary angiographic views. Angiotensinogen gene molecular variants were designated AA , Aa , and aa . The a allele indicated thymine-cytosine transition at nucleotide 704 in exon 2. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction was performed to amplify the concerned region of the angiotensinogen gene. After restriction enzyme digestion, it was possible to distinguish the molecular variant of the angiotensinogen gene. The frequencies of these genotypes were 7.3%, 26.8%, and 65.9% in the patients and 18.8%, 31.9%, and 49.3% in the control subjects for the AA , Aa , and aa allelles, respectively. There was an excess in the a allele among patients ( P <.01). Conclusions We found a significant association between coronary atherosclerosis and a molecular variant of the angiotensinogen gene. The results suggested that the molecular variant of the angiotensinogen gene could be a new risk factor for coronary atherosclerosis.