MOLECULAR VARIANT OF ANGIOTENSINOGEN GENE IS ASSOCIATED WITH CORONARYATHEROSCLEROSIS

Background A positive association was previously reported between angi otensin-converting enzyme (ACE) gene polymorphism and several cardiova scular diseases, such as myocardial infarction, left ventricular hyper trophy, and restenosis after percutaneous transluminal coronary angiop lasty. Plasma ACE activity and carotid-wall thickening measured by ult rasonography were related, and it was postulated that long-term exposu re to high levels of plasma ACE could be involved in structural change s of the arterial wall. In addition, angiotensinogen gene mutation was recently reported to be associated with essential hypertension and pr eeclampsia. There exists a possibility that the renin-angiotensin syst em plays an important role in the progress of cardiovascular diseases in humans. Therefore, we examined the association between the molecula r variant of the angiotensinogen gene and coronary atherosclerosis. Me thods and Results This study included 82 patients who had coronary ath erosclerosis and 160 control subjects; all study participants were Jap anese. All patients with coronary atherosclerosis had at least one cor onary artery with >25% luminal diameter obstruction on average accordi ng to multiple coronary angiographic views. Angiotensinogen gene molec ular variants were designated AA, Aa, and aa. The a allele indicated t hymine-cytosine transition at nucleotide 704 in exon 2. Genomic DNA wa s extracted from peripheral blood leukocytes. Polymerase chain reactio n was performed to amplify the concerned region of the angiotensinogen gene. After restriction enzyme digestion, it was possible to distingu ish 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 al lelles, respectively. There was an excess in the a allele among patien ts (P<.01). Conclusions We found a significant association between cor onary atherosclerosis and a molecular variant of the angiotensinogen g ene. The results suggested that the molecular variant of the angiotens inogen gene could be a new risk factor for coronary atherosclerosis.