ASSOCIATION OF GENETIC POLYMORPHISMS IN THE ACE, APOE, AND TGF-BETA GENES WITH EARLY-ONSET ISCHEMIC-HEART-DISEASE

Background: The genetic factors that contribute to ischemic heart dise ase (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apo lipoprotein E (ApoE) have been implicated independently in the risk of IHD. Hypothesis: This study examined whether genetic poly morphisms i n the ACE and ApoE genes are associated with early onset IHD. Polymorp hisms in a third gene, transforming growth factor beta 2 (TGF beta 2), with a known role in wound repair and cardiac development, are also e xamined with respect to early onset IHD. Methods: In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years fo r women, and 100 controls with angiographically confirmed normal coron ary arteries were recruited for this study. The ACE, ApoE, and TGF bet a 2 genotypes were determined by polymerase chain reaction amplificati on or Southern blotting and were compared with the patient's clinical and family histories. Results and Conclusion: The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reducti on in the number of patients with the DD genotype (patients: 24% DD, c ontrols: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributin g to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, fa mily history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset MD. There was no evidence for a synergistic effect between the ACE and ApoE gen otypes on the risk of early onset IHD. A polymorphism in the TGF beta 2 gene was rare and nor associated with early onset IHD.