Association of genetic mutations and polymorphisms with coronary artery disease

Abstract Introduction Genetic mutations and polymorphisms in interaction with environmental factors are responsible for occurrence of coronary artery disease (CAD) in young population. Aim To determine and compare the allelic and genotypic frequencies of the analyzed gene variants of selected genes between patients with CAD and healthy individuals, and to determine the probability of occurrence of CAD in carriers of certain genetic mutations and polymorphisms. Material and methods This clinical study analyzed the demographic, clinical, and genetic data of a group of 89 patients with CAD versus control group of 90 healthy subjects. All of the subjects were in age range of 18-50 years. The selection was with previously established inclusion and exclusion criteria. Inclusion criteria for the group with CAD were: patients with angina pectoris or acute coronary syndrome due to CAD proven by coronary angiography. For comparison, a control group of healthy individuals without CAD were recruited randomly, representing the general population and consisting of an appropriate number of male and female individuals, with an average age similar to the other group. Exclusion criteria for both groups were: younger than 18 or older than 50 years, pregnant women, type 1 diabetes mellitus, valvular disease, cardiomyopathies, congenital heart defects, active malignant disease, acute or chronic inflammatory or infectious disease etc. To determine the genotype, genetic testing was performed on each patient. A multiplex polymerase chain reaction (PCR) was performed to amplify the genes, and the genotype of the subject was determined. The following genes were analyzed: Factor V (Leiden and R2), Prothrombin (G20210A), β-Fibrinogen (-455 GA), Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C), Factor XIII, Endothelial protein C receptor (EPCR A4600G and G4678C), Endothelial nitric oxide synthase (eNOS 786 TC and G894T), Lymphotoxin Alpha (LTA), Β-fibrinogen, Human platelet antigen (HPA1), Angiotensin converting enzyme (ACE), Apolipoprotein (APO B and E), Plasminogen Activator Inhibitor (PAI)-1. Results From the results we noticed that following gene mutations and polymorphisms are significantly more prevalent in the patients with CAD: homozygous variant for eNOS-786 TC (p=0.0001), and heterozygous for LTA (p=0.01). (Picture 1 and 2) Homozygotes for eNOS-786 TC have 9.2 times significantly higher probability of developing CAD compared to patients with normal genotype OR=9.21 95% CI (2.52-33.66). Heterozygous carriers for LTA have 2.17 times significantly higher probability of developing CAD compared to individuals without gene mutation OR=2.17 95% CI (1.15-4.09). Homozygous variant for eNOS- G894T was only present in the patient group with CAD. Conclusions We concluded that there is a significant association with the presence of homozygous variants of eNOS (786 TC or G894T), as well as the heterozygous variant of LTA with the occurrence of CAD.Gene grequencies of eNOS 786 TC Gene grequencies of LTA