Effects of ACE polymorphisms and other risk factors on the severity of coronary artery disease.

Coronary artery disease (CAD) is a multifactorial disease influenced by genetic and environmental factors. Major risk factors of CAD are hypertension, hyperlipidemia, smoking, family history and obesity. Also polymorphisms in the angiotensin-I converting enzyme (ACE) gene can associate with CAD. The relationship between ACE polymorphisms and other risk factors is not well understood in CAD, likely due to the complex interrelation of genetic and environmental risk factors. The aim of this study was to investigate the associations of CAD risk factors and ACE polymorphisms in patients with CAD. We enrolled 203 consecutive patients and 140 healthy subjects in the study. The severity of CAD was evaluated according to the number of vessels with significant stenosis. ACE insertion (I)/deletion (D) genotype was determined by PCR. The frequency of the DD genotype was significantly higher in patients. D allele frequency was higher among CAD subjects when compared to the control group. The number of stenotic vessels were found to be statistically associated with a high frequency of DD polymorphism and D allele and a low frequency of I allele in patients, especially in male patients. The control group displayed II and ID genotypes more frequently than did the patients. The ACE I/D genotype was associated with hyperlipidemia and smoking history. We consider that the DD polymorphism and D allele may affect the severity of CAD, while I allele may have a protective effect. In conclusion, the ACE I/D genotype may interact with conventional risk criteria in determining the risk of CAD.

Multifactor dimensionality reduction analysis of MTHFR, PAI-1, ACE, PON1, and eNOS gene polymorphisms in patients with early onset coronary artery disease.

BACKGROUND: Association studies in the Turkish population have investigated the single locus effects of different gene polymorphisms on coronary artery disease (CAD). CAD is a complex polygenic disease that involves complex interactions among multiple genetic and environmental conditions. DESIGN: We evaluated associations of five candidate genetic polymorphisms (methylene tetrahydrofolate reductase C677T, plasminogen activator inhibitor 4G/5G, endothelial nitric oxide synthase (eNOS) 3-27 base pair repeat, insertion, or deletion of a 287 bp Alu repeat sequence polymorhism of angiotensin I converting enzyme, and paraoxonase Gln192Arg PON1 polymorphisms) with the presence and extent of early onset CAD. METHODS: DNA was isolated and amplified from 90 consecutive patients with angiographically proven early onset CAD (ages 41 ± 5 for men, 49 ± 7 for women) and also from 90 control subjects with no significant coronary obstruction angiographically (ages 42 ± 5 for men, 48 ± 6 for women). Multifactor dimensionality reduction (MDR) analysis was performed to identify a model of CAD based on both genetic and conventional risk factors. RESULTS: MDR analysis detected a significant model with four genes (prediction success ∼ 61%, p = 0.03). When the total number of the conventional risk factors is analysed with the candidate polymorphisms, a different model is identified that includes three of the four genes from the above model and achieves a similar prediction of CAD as the gene only model. CONCLUSION: These data indicate that gene-gene and gene-environmental risk interactions form significant models in predicting early onset CAD.