(Circulation. 1995;92:1808-1812.)
© 1995 American Heart Association, Inc.
Articles |
Angiotensin-I Converting Enzyme Genotypes and Left Ventricular Hypertrophy in Patients With Hypertrophic Cardiomyopathy
From the Division of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Tex (M.L., M.A.Q., R.H., Q.T.Y., R.R., A.J.M.) and Division of Cardiology and the Center for Cardiovascular Research, the Toronto Hospital, Ontario, Canada (A.O., H.R., D.W., C.C.L., M.S.).
Background The variability of the phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) indicates a potential role for additional modifying genes. Variants of angiotensin-I converting enzyme (ACE) gene have been implicated in cardiac hypertrophy. To assess whether ACE genotypes influence the phenotypic expression of hypertrophy, we determined the left ventricular mass index (LVMI) and extent of hypertrophy in 183 patients with HCM.
Methods and Results LVMI was derived by the area-length method using two-dimensional echocardiograms. Extent of LVH was determined by a point score method (1 to 10 points). DNA was extracted from blood, and ACE genotyping was performed by polymerase chain reaction (PCR) with an established protocol. Amplification of DNA in the region of polymorphism by PCR of alleles I and D showed 490- and 190-bp products, respectively. ACE genotypes DD, ID, and II were present in 60, 90, and 33 patients with HCM, respectively. In genetically independent patients (n=108), the mean LVMI (g/m2) was 148±35.3 in those with DD (n=35) and 134.2±33.3 in those with ID and II (n=73) genotypes (P=.046). LVH score was 6.69±1.71 in patients with DD and 5.55±2.19 in those with ID and II genotypes (P=.004). Regression analysis showed that ACE genotypes accounted for 3.7% and 6.5% of the variability of LVMI and LVH score (P=.046 and P=.008, respectively). In 26 patients from a single family, LVMI and LVH score were also greater in patients with DD than in those with ID and II genotypes. ACE genotypes accounted for 14.7% and 10.4% of the variability of the LVMI and extent of hypertrophy, respectively.
Conclusions ACE genotypes influence the phenotypic expression of hypertrophy in HCM.
Key Words: angiotensin • enzymes • cardiomyopathy • hypertrophy • genes
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|
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