S Wang1, J Wang, Y Zou, J Wang, H Wang, R Hui. 1. The First Geriatric Cardiology Department, Chinese Peoples' Liberation Army General Hospital, 167 Beilishi Road, 100037, Beijing, China.
Abstract
BACKGROUND: Variations of angiotensinogen (AGT) gene have been associated with cardiac hypertrophy. We hypothesized that AGT gene polymorphism may play a modifier role in the diversity of left ventricular outflow obstruction. METHODS: The polymorphisms of the AGT gene were genotyped in 225 patients with hypertrophic cardiomyopathy (HCM) and 243 age-and sex-matched healthy controls. The effect of the A and G alleles on the expression of the reporter gene were evaluated in vitro using dual-luciferase reporter assays. RESULTS: Our results showed that the frequency of the A allele was higher in patients than in controls (50.2 % vs. 35.8 %, p < 0.05). Patients carrying the AA and AG genotypes had a higher proportion of left ventricular outflow obstruction (30.1 % vs. 17.0 %, p < 0.05) and heart failure (NYHA functional class III ~ IV, 35.4 % vs. 18.8 %, p < 0.05) than those carrying the GG genotype had. After adjusted for age, sex, the thickness of the interventricular septum, family history of HCM, and sudden death, the A allele conferred a 2.4-fold risk for left ventricular outflow obstruction than the GG genotype did (adjusted OR = 2.4, 95 %CI 1.2-4.8). The G allele suppressed the expression of the reporter gene significantly compared with the A allele (p < 0.05). CONCLUSION: AGT gene variations may be genetic modifiers for the development of HCM.
BACKGROUND: Variations of angiotensinogen (AGT) gene have been associated with cardiac hypertrophy. We hypothesized that AGT gene polymorphism may play a modifier role in the diversity of left ventricular outflow obstruction. METHODS: The polymorphisms of the AGT gene were genotyped in 225 patients with hypertrophic cardiomyopathy (HCM) and 243 age-and sex-matched healthy controls. The effect of the A and G alleles on the expression of the reporter gene were evaluated in vitro using dual-luciferase reporter assays. RESULTS: Our results showed that the frequency of the A allele was higher in patients than in controls (50.2 % vs. 35.8 %, p < 0.05). Patients carrying the AA and AG genotypes had a higher proportion of left ventricular outflow obstruction (30.1 % vs. 17.0 %, p < 0.05) and heart failure (NYHA functional class III ~ IV, 35.4 % vs. 18.8 %, p < 0.05) than those carrying the GG genotype had. After adjusted for age, sex, the thickness of the interventricular septum, family history of HCM, and sudden death, the A allele conferred a 2.4-fold risk for left ventricular outflow obstruction than the GG genotype did (adjusted OR = 2.4, 95 %CI 1.2-4.8). The G allele suppressed the expression of the reporter gene significantly compared with the A allele (p < 0.05). CONCLUSION:AGT gene variations may be genetic modifiers for the development of HCM.
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