The Study Of Association Between Angiotensin Converting Enzyme Gene Polymorphism And Forward Prognosis In Chinese Patients With Sporadic Hypertrophic Cardiomypathy

Background: Hypertrophic cardiomyopathy (HCM) is a common disease which represents a main cause of sudden cardiac death. Despite extensive physiologic investigation,the primary determinants of HCM, as well as the factors which determine specific clinical outcomes, such as left ventricular hypertrophy and remodeling, remain unknown. The rennin-angiotensin system (RAS) has an independent direct role in modulating cardiac growth. There have been a few reports about insertion / deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in patients with HCM but the results remained controvertial. By now, little has been reported abort the study of association between the I/D polymorphism of ACE gene and forward prognosis in patients with sporadic hypertrophic cardiomyopathy (SHCM).Objective: The aim of the study was to analyse: 1.The distribution of the I/D polymorphism of ACE gene in Chinese patients with SHCM.2.The association between the ACE genotype and left ventricular hypertrophy (LVH) or remodeling in patients with SHCM.3. The influence of the ACE genotype on the intermediate phenotype of ACE. 4.The association between the ACE gene I/D polymorphism and the phenotype of ventricular arrthymia in patients withSHCM.5.The association between the ACE gene I/D polymorphism and curative effect of ACE inhibitor (ACEI) and beta-adrenergic blocker in patients with SHCM. 6.The association between the ACE gene I/D polymorphism and forward prognosis in patients with SHCM. Methods:1. 200 subjects were examined including 98 normal individuals (group I), aged 18-65 years, and 102 patients with SHCM(group II), aged 20-68 years.2. Investigate and record the case history of the subjects such as hypertension, diabetes, mellitus, renal disease etc . especially the family history of HCM.3. Perform systemic physical examination and record the body height, body weight to calculate the body surface area(BSA).4. Determine the serum total cholesterol (TC), triglyceride(TG)> blood glucose, ACE and so on.5. Assess left ventricular mass(LVM) and geometry with sonarography in HCM. Two-dimensional echocardiography was performed and images of the left ventricle were obtained in the parasternal long-axis and short-axis and apical two-chamber and four-chamber riews. The magnitude of LVH was determined by calculating echocardiographic LVM by the area-length method as recommended by the American Society of Echocardiography and was indexed to BAS(LVMI) . The extent of hypertrophy was also assessed by a semi-quantitative point score method developed by Wigle et al, in which it was to reflect truly the extent of asymmetric hypertrophy.6. The insertion/deletion(I/D) polymorphism of ACE gene was studied using polymerase chain reaction(PCR) and restriction fragment length polymorphism (RFLP).7. Ventricular arrthymia recorded with 24 hours monitoring system typed PI200Amadeby US-A.8. The patients with SHCM were divided into three groups by differentgenotypes,such as DD,ID,II. Each group was treated with different drugs including ACEI , beta-blocker and combined administration.9. After five years, the curative effect of the drugs and forward prognosis were evaluated by echocardiography and analysis of mortality .10. Statistical methods: Results were expressed as X ± S . T test, X2 test ,ANOVA and analysis of covariance of SPSS 10.0 soft ware were used to evaluate the difference among groups.Multivariate linear stepwise regression analysis of SPSS 10.0 was used,too .Results:1. Higher frequency of DD genotype and rare D allele were found in HCM patients compared with controls (P<0.05).2. LV mass index (LVMI) and the left Ventricular hypertrophy score (LVHS) were calculated in HCM patients. After adjustment for other covariables, the DD genotype was associated with significantly higher LVMI and LVHS than those in II genotype. On multiple regression analysis, the ACE genotypes were independently related to LVMI and L...