Abstract 2398: Polymorphisms of Angiotensin Converting Enzyme and Endothelial Nitric Oxide Synthase Genes Act Synergistically to Increase the Risk of Cardiovascular Events in Patients with Hypertrophic Cardiomyopathy

Abstract

Background: Patients with hypertrophic cardiomyopathy (HCM) have a small left ventricular cavity size due to hypertrophy. Therefore, reduction of venous return and intravascular volume in patients with HCM leads to low cardiac output and hypotension. We reported that the angiotensin converting enzyme insertion/insertion (ACE I/I) genotype, which leads to inhibitory renin-angiotensin system, is a significant risk factor for cardiovascular events (CE) in patients with HCM. Recently, the endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298Asp), which plays an important role in the modulation of cardiovascular physiology, is reported to be associated with heart diseases. Methods and Results: Genotyping at these loci was performed in 150 patients with HCM. This study design was a nested case-control study. The cardiovascular events were defined as cardiac death and hospitalization for stroke or congestive heart failure. Patients were divided into two groups: group A of 44 patients (29%) with one or more history of the cardiovascular events and group B of 106 patients (71%) without history of the cardiovascular events. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of CE. The odds ratio for cardiovascular events among persons who had ACE I/I genotype as compared with those with the other ACE genotypes was 2.5 (P < 0.01). In a dominant Asp allele model of the eNOS gene polymorphism, there was a significant difference in genotypes between the two groups (p < 0.01). In addition, there was a marked increase in the risk of CE among persons who were homozygous for both genotypes (ACE I/I and eNOS 298Glu/Glu) (odds ratio, 2.7, P < 0.01). Conclusion: The ACE I/I and eNOS 298Glu/Glu act synergistically to increase the risk of CE in patients with HCM. Genotyping at these two loci may be a useful approach for identification of persons with HCM at risk for CE.