Angiotensin-Converting Enzyme, Angiotensin II Receptor, Apolipoprotein E and Endothelial Constitutive Nitric Oxide Synthase Gene Polymorphisms in Dilated Cardiomyopathy

Genetic factors are hypothesized to contribute to the dilated cardiomyopathy (DCM) susceptibility, even in sporadic cases. Abundant reports have investigated the association between various gene polymorphisms and the phenotypic expression of DCM. The aim of the present study is to assess the effect of four candidate gene polymorphisms (1166 A/C polymorphism of the angiotensin II type 1 receptor (AGTR1) gene, I/D polymorphism of angiotensin converting enzyme (ACE) gene, endothelial nitric oxide synthase (ec-NOS) and apolipoprotein E (APOE genes) on the pathogenesis of dilated cardiomyopathy. We studied 76 consecutive patients (mean age 58±12) with DCM and 88 healthy age- and sex-matched control subjects (mean age 59±12). All patients were assessed by 2-dimensional echocardiography and all had left ventricular dilatation (end diastolic diameter >55 mm) and impaired systolic function (ejection fraction <40%). All patients were catheterized. Patients having normal coronary arteries were classified as 'idiopathic' and the remaining group as 'ischemic' DCM. Patients with specific heart muscle disease, isolated right ventricular dilatation and valvular or pericardial disease were excluded. Deoxyribonucleic acid (DNA) was isolated from blood samples, and genotypes were determined by specific polymerase chain reaction (PCR) and separation of amplified fragments by agarose gel electrophoresis. We compared genotypes and allele frequencies, echocardiographic measurements, biochemical variables in our patients and control group. Age, sex, body mass index differences were statistically non-significant. APO E genotypes and allele frequencies were significantly different in patients with DCM. Multiple regression analyses demonstrated lack of independent association. Subgroup analysis revealed that the four candidate gene polymorphisms were not associated with ischemic or idiopathic DCM.
CONCLUSIONS
No significant association exists between dilated cardiomyopathy and polymorphism of the AGTR1, ACE, ecNOS and APOE gene polymorphisms. (Türk Kardiyol Dern Arş 2004; 32: 295-301)