Pharmacogenomics of cardiovascular diseases

Abstract

Recent progress in the Human Genome Project has explored the pathophysiology of common cardiovascular diseases from the aspect of pharmacogenomics. Using a high through-put analyzer and genetic epidemiology, T235 allele of the angiotensinogen gene has been reported to associate with essential hypertension itself or patient's family history of hypertension. The magnitude of the effect of this hypertensive allele of the angiotensinogen gene on blood pressure depends on the sodium intake of individual patients. On the other hand, the positive correlation between blood pressure and body mass index is affected by the GIn27Glu genotype of the β2-adrenoceptor gene. Furthermore, the active type of acetaldehyde-dehydrogenase gene indirectly increases blood pressure in association with high alcohol intake compared to the inactive type of the gene. More recently, some pharmacogenetic studies showed close interactions between the genes of the renin-angiotensin system and effectiveness of therapy. The angiotensin converting-enzyme (ACE) I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after percutaneous transluminal coronary angioplasty. We found that, in our outpatient department of Osaka University Hospital, the efficacy of medication was 12% lower in subjects with ACE/DD than in those with ACE/ID+II, irrespective of the type of antihypertensive drugs. These results suggest that antihypertensive medications should be modified according to the patient's genotypes. In conclusion, the growing knowledge added by ongoing toxicogenomic and pharmacogenomic studies is having an impact at the bedside, to establish new individualized "tailor-made medicine".