Genetic risk factors for coronary artery disease in patients with ischaemic cardiomyopathy

The angiotensin converting enzyme (ACE) gene DD genotype and the human paraoxonase/arylesterase (HUMPONA) BB genotype have been reported to be associated with coronary artery disease (CAD). We determined the prevalence of both polymorphisms in patients with ischaemic cardiomyopathy (ISC) compared to a normal population and sought associations with coronary atherosclerosis and left ventricular dysfunction. Methods: 100 patients were genotyped for the ACE polymorphism including 50 for the Humpona gene polymorphism. All patients had either ECG evidence of myocardial infarction and/or CAD demonstrated by coronary angiography. Left ventricular (LV) function and dimensions were obtained by echocardiography. Patients were genotyped for both gene polymorphisms by the polymerase chain reaction (PCR) technique using genomic DNA obtained from white cells and specific flanking primers. The PCR products were resolved (after digestion with the restriction enzyme Alw1 for Humpona genotyping) by agarose gel dectrophoresis. Results: The HUMPONA BB genotype was present in 11% of patients and controls (n=100, P=NS). The ACE DD genotype was more common in patients (40% vs 24%, p<0.05). The angiographic Humpona subgroup (39/50) showed more 3 vessel CAD in HUMPONA AA genotype patients compared with AB/BB group (78% vs 42%, p<0.05, independent of total cholesterol, smoking and diabetes). The mean left ventricular end diastolic dimensions for patients with II, ID and DD ACE genotypes were similar. Conclusions: Both the ACE and HUMPONA genotypes are important markers in patients with ISC. The ACE DD genotype is more common in these patients but does not influence the degree of ventricular dilatation. The HUMPONA AA genotype is independently associated with more severe CAD in ISC patients.