Abstract 265: Genetic Polymorphisms in Angiotensinogen Gene as Potential Modifiers of Hypertrophic and Dilated Cardiomyopathy Phenotypes

Abstract

Background: Hypertrophic Cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) are diseases of mutant sarcomeric proteins. However, there is marked variation in disease severity and progression, even among patients with identical causal mutation. The renin- angiotensin system plays a major role in the pathophysiology of heart failure and genetic variations in these genes may modulate the risk of disease and be partly responsible for the disease heterogeneity and severity. OBJECTIVE: To evaluate the association of angiotensinogen (AGT) gene polymorphisms (T174M and M235T) with risk of developing severe disease phenotype in HCM and DCM patients. MATERIAL AND METHODS: 275 prospectively enrolled patients (122 HCM and 153 DCM) and 200 normal controls were genotyped for T174M and M235T polymorphisms of AGT gene. Effect of AGT genotypes on interventricular septum thickness and left ventricular ejection fraction (LVEF) were analyzed using linear regression model. RESULTS: We observed significantly higher prevalence of 235T allele in DCM patients which was associated with increased risk of DCM (OR 2.37, CI 1.07-5.25, p=0.04), however T174M polymorphism did not show a significant association with risk of DCM (OR 1.1, CI 0.65-1.84, p=0.79). The frequency of 174M allele was significantly higher in HCM patients as compared to controls and associated with increased risk of HCM (OR 1.95, CI 1.16-3.25, p=0.01), but no significant association of M235T polymorphism was observed with HCM (OR=1.10, CI 0.54-2.22,p=0.8). We did not observe any significant difference in mean LVEF in DCM patients carrying either M235 allele or 235T allele (M235: 27.22±7.13; 235T: 28.60±10.40; p=0.6) or carrying T174 allele or 174M allele (28.83±10.34 vs 28.09±9.93; p=0.7). No significant difference in left ventricular hypertrophy (LVH, mean septal thickness) was observed between 235T and M235 allele carriers [(24.07±5.16mm vs 23.26±6.04mm, p=0.6] or between 174M and T174 allele carriers (T174: 23.41±5.12mm, 174M: 22.83±7.17mm; p=0.6) in HCM patients. CONCLUSION: The variant AGT M235T and AGT T174M alleles confer increased risk of DCM and HCM respectively, but do not appear to be associated with disease severity or progression in these patients.