Analysis of Twelve Cardiovascular Disease Related Gene Mutations among Turkish Patients with Coronary Artery Disease

Abstract

Background: Coronary artery disease (CAD) is a multifactorial disorder. It is important to identify gene mutations that may be responsible for the development of CAD. The aim of this study was to determine the frequency of twelve cardiovascular disease (CVD) related gene mutations in coronary artery patients. Methods:The CVD StripAssay (Vienna Lab, Austria) was performed to analyze the twelve gene mutations on 52 coronary artery patients and 39 healthy controls. After DNA isolation from blood samples, hybridization with biotin marked probes was performed to PCR products containing the related region of mutant genes. Chisquare tests were used for statistical analyses.Results: Any differences were not observed between coronary artery patients and healthy controls in terms of the frequencies of studied twelve gene mutations except MTHFR A1298C mutation. It was observed that heterozygous and homozygous mutant genotypes of MTHFR A1298C mutation have protective effects against coronary artery disease [p = 0.06, in 95% CI OR = 0.205 (0.0421-1.001)]. Although all the three genotypes of PAI-1 4G/5G, ACE I/D and MTHFR C677T mutations were observed in both groups; homozygous mutant genotypes weren't observed for the Factor V Leiden, Factor V H1299R, Prothrombin G20210A, Factor XIII V34L, β-Fibrinojen -455G > A, HPA-1 1a/1b mutations in any of the groups. Heterozygote and homozygote mutant genotypes of APOB R3500Q mutation was not seen in both groups. When the patient group was evaluated in terms of compound genotypes, the rate of two mutations (ACE I/D, MTHFR A1298C) was 56%, the rate of three mutations (PAI-1 4G/5G, MTHFR A1298C, ACE I/D) was 53%, the rate of four mutations (PAI-1 4G/5G, MTHFR A1298C, HPA-1 1a/1b, ACE I/D) was 33%. High cholesterol, the number of clogged arteries and smoking rates was high in CAD patients with compound genotypes or carrying mutations in multiple genes compared the others. Conclusion:Among 12 studied gene mutations, only the MTH-FR A1298C mutation was determined to have a protective effect against CAD. In addition, cumulative effects of the mutant genotypes and environmental factors on people with the combined genotypes may be trigger for CAD.

Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis

“…For both mutations, no homozygous cases were identified. In other studies, assessing different ethnic groups, the frequency of heterozygous FV Leiden genotype ranged between 2% and 4% in healthy individuals [ 29 , 37 ], whereas in patients with coronary artery disease, it was 3.7% [ 29 ]. Furthermore, a frequency of 9.5% to 16.5% for FV R2 heterozygosity was shown in patients with VTE, in contrast to 5.8% to 10.4% in the general population, having a fluctuation in the proportion due to different ethnicities and sample sizes [ 38 , 39 , 40 ].…”

“…The prothrombin G20210A variant is correlated with elevated prothrombin levels in plasma, leading to an increased rate of thrombin generation and activation [ 42 ]. Studies in patients with coronary artery disease found a low frequency (3.3%) of the prothrombin G20210A heterozygous genotype, whereas the homozygous genotype was not identified [ 29 ]. Similarly, patients who developed thromboembolic episodes showed low frequency for the G20210A heterozygous genotype, and no homozygous individual was identified [ 7 ].…”

“…In addition, the results of the analysis of the HPA-1 polymorphisms in the groups studied showed that only HPA-1a/1a and HPA-1a/1b genotypes were detected, whereas nonhomozygous individuals for the 1b allele were identified. Earlier studies in patients with coronary artery disease reported the presence of HPA-1a/1a and HPA-1a/1b genotypes in the study participants, whereas only HPA-1a/1a was identified in the control group [ 29 ]. In contrast, screening Greek Cypriots from the general population showed the presence of the HPA-1b/1b variant at a frequency of 4%, and this supports the notion of further analysis of such polymorphisms to better validate the results [ 6 ].…”

“…In contrast, screening Greek Cypriots from the general population showed the presence of the HPA-1b/1b variant at a frequency of 4%, and this supports the notion of further analysis of such polymorphisms to better validate the results [ 6 ]. Interestingly, the 1b allele has been associated with the early onset of MI and ischemic stroke, and this has been demonstrated by a large case-control study including 1211 patients from Germany and 510 patients from the U.S.A. with coronary artery disease in which participants carrying the 1b allele had an increased risk of early onset of MI [ 29 ].…”

“…Furthermore, predisposition to stroke, myocardial infarction (MI), or coronary artery disease was correlated with human platelet antigen (HPA-1) 1a/b polymorphisms [ 28 , 29 ], whereas MI was further associated with mutations linked to the gene that codes the angiotensin-converting enzyme (ACE) [ 29 ].…”