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Molecular variant of angiotensinogen gene is associated with coronary atherosclerosis
T Ishigami1, S Umemura, T Iwamoto
1Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Insights
A specific angiotensinogen gene variant is linked to coronary atherosclerosis in Japanese individuals. This finding suggests the angiotensinogen gene molecular variant may be a novel risk factor for this cardiovascular disease.
Area of Science:
- Cardiovascular Genetics
- Molecular Biology
- Human Genetics
Background:
- Previous studies linked angiotensin-converting enzyme (ACE) gene polymorphism to cardiovascular diseases.
- High plasma ACE activity may contribute to arterial wall structural changes.
- Angiotensinogen gene mutations have been associated with hypertension and preeclampsia, suggesting a role for the renin-angiotensin system in cardiovascular disease.
Purpose of the Study:
- To investigate the association between angiotensinogen gene molecular variants and coronary atherosclerosis.
- To determine if specific angiotensinogen gene variants are risk factors for coronary atherosclerosis.
Main Methods:
- The study included 82 Japanese patients with coronary atherosclerosis and 160 Japanese control subjects.
- Genomic DNA was extracted from leukocytes, and the angiotensinogen gene region was amplified using polymerase chain reaction.
- Molecular variants (AA, Aa, aa) were identified after restriction enzyme digestion, with the 'a' allele representing a specific thymine-cytosine transition.
Main Results:
- The frequencies of angiotensinogen genotypes differed significantly between patients and controls.
- An excess of the 'a' allele was observed in patients with coronary atherosclerosis (P < .01).
- Genotype frequencies were 7.3% AA, 26.8% Aa, 65.9% aa in patients versus 18.8% AA, 31.9% Aa, 49.3% aa in controls.
Conclusions:
- A significant association was found between coronary atherosclerosis and a molecular variant of the angiotensinogen gene.
- This molecular variant of the angiotensinogen gene may represent a new risk factor for coronary atherosclerosis.
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 angiotensin 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 alleles, 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 angiotensin gene. The results suggested that the molecular variant of the angiotensinogen gene could be a new risk factor for coronary atherosclerosis.