ABSTRACT
Angiotensin-converting enzyme (ACE) activity and polymorphism contribute significantly to the prognosis of patients with cardiomyopathy. The aim of this study was to determine the activity and type of ACE polymorphism in patients with familial and nonfamilial hypertrophic cardiomyopathy (HCM) and to correlate these with echocardiographic measurements (echo-Doppler). We studied 136 patients (76 males) with HCM (69 familial and 67 nonfamilial cases). Mean age was 41 ¡À 17 years. DNA was extracted from blood samples for the polymerase chain reaction and the determination of plasma ACE levels. Left ventricular mass, interventricular septum, and wall thickness were measured. Mean left ventricular mass index, interventricular septum and wall thickness in familial and nonfamilial forms were 154 ¡À 63 and 174 ¡À 57 g/m2 (P = 0.008), 19 ¡À 5 and 21 ¡À 5 mm (P = 0.02), and 10 ¡À 2 and 12 ¡À 3 mm (P = 0.0001), respectively. ACE genotype frequencies were DD = 35%, ID = 52%, and II = 13%. A positive association was observed between serum ACE activity and left ventricular mass index (P = 0.04). Logistic regression showed that ACE activity was twice as high in patients with familial HCM and left ventricular mass index ¡Ý190 g/m2 compared with the nonfamilial form (P = 0.02). No other correlation was observed between ACE polymorphisms and the degree of myocardial hypertrophy. In conclusion, ACE activity, but not ACE polymorphisms, was associated with the degree of myocardialhypertrophy in the patients with HCM.
Subject(s)
Adult , Female , Humans , Male , Cardiomyopathy, Hypertrophic/enzymology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Polymorphism, Genetic/genetics , Cardiomyopathy, Hypertrophic, Familial/enzymology , Cardiomyopathy, Hypertrophic, Familial/genetics , Cardiomyopathy, Hypertrophic, Familial , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic , Echocardiography, Doppler , Genotype , Hypertrophy, Left Ventricular , Phenotype , Severity of Illness IndexABSTRACT
Human angiotensin converting enzymcC4CE) gene displays an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by presence or absence of a 287-bp fragment of DNA; II, ID and DD genotype. DD genotype has been suggested as a risk factor of various cardiovascular diseases and chronic nephropathies such as IgA nephropathy and diabetic nephropathy. This study was designed to investigate if the ACE polymor-phism is related to the clinical and pathologic findings of minimal change nephrotic syndrome(MCNS) and focal segmental glomerulosclerosis(FSGS) in children. Ninety children with primary nephrotic syndrome(MCNS and steroid responsive nephrotic syndrome : 68 cases, FSGS; 22 cases) and 97 healthy normal controls were examined. The genotype for the polymorphism was determined by PCR method. The distribution of ACE genotypes in primary nephrotic syndrome(II 28.6%, ID 53.8%, DD 17.6%) was not different from that in controls(II 39.2%, ID 41.2%, DD 29.6%). The IJ genotype was more frequent in FSGS(II 64.7%, ID 23.5%, I)D 11.8%) than in MCNS and steroid responsive nephrotic syndrome(I 20.3%, ID 60.8%, DD 18.9%, p<0.03). The ACE genotypes were not associated either with frequency of relapse in MCNS or steroid responsive nephrotic syndrome or with presence of hypertension, responsiveness to steroid therapy and progression of renal dysfunction in FSGS. We concluded that deletion polymorphism of ACE gene is not associated with increased risk for renal progression in children with primary nephrotic syndrome.
Subject(s)
Child , Humans , Angiotensins , Cardiovascular Diseases , Diabetic Nephropathies , DNA , Genotype , Glomerulonephritis, IGA , Hypertension , Introns , Nephrotic Syndrome , Peptidyl-Dipeptidase A , Polymerase Chain Reaction , Recurrence , Risk FactorsABSTRACT
BACKGROUND: The angiotensin-converting enzyme(ACE) plays an important role in cardiovascular disease by production of angiotensin and degradation of bradykinin. Cloning of ACE gene revealed an insertion/deletion(I/D) polymorphism according to the presence/absence of a 287 base pair fragment in the 16th intron of ACE gene, and the ACE polymophism was associated with ACE activity. The genotype DD was identified as a risk factor for myocardial infarction in several studies. We analyzed the ACE I/D polymorphism in 62 patients with myocardial infarction and 67 normal subjects. METHODS: Genomic DNA from peripheral blood was amplified by polymerase chain reaction and characterized by three ACE genotypes; two insertion alleles(genotype II), two deletion alleles(genotype DD) and heterogenous alleles(genotype ID). ACE activity was determined by spectrophotometric method utilizing the synthetic substrate. RESULTS: There was no significant difference in ACE polymorphism between patients and normal subjects. But, the frequency of genotype DD was significantly increased in the low-risk group of patients compared with the high-risk group. The multi-vessel disease was more strongly associated with genotype DD, but there was no statistical significance. The ACE activity was strongly associated with ACE polymorphism with the activity being highest in genotype DD. There was no significant difference between patients and control subjects of the same genotype. CONCLUSION: There was no significant difference in ACE polymorphism between patients and normal subjects. The frequencies for genotype II, ID, DD were 0.328, 0.537, 0.134, respectively in normal subjects. There was high frequency of genotype II compared with Caucasians. A deletion polymorphism(genotype DD) may increase the risk for myocardial infarction in lowrisk group, and the serum ACE activity was correlated with three genotypes.