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Endothelin-converting Enzyme-1b Genetic Variants Increase the Risk of Coronary Artery Ectasia
Gulcin Ozkara1,2, Ezgi Irmak Aslan3,4, Fidan Malikova3
1Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. gulcinozkara@gmail.com.
Insights
Genetic variations in the endothelin converting enzyme-1b (ECE-1b) gene, specifically rs213045 and rs2038089, are associated with an increased risk of coronary artery ectasia (CAE). This association is modified by the presence of type II diabetes.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Epidemiology
Background:
- Coronary artery ectasia (CAE) is characterized by abnormal coronary artery enlargement, often linked to atherosclerotic coronary artery disease (CAD).
- Endothelin converting enzyme-1 (ECE-1) plays a crucial role in regulating endothelin-1 (ET-1), a potent vasoconstrictor involved in vascular pathologies.
- Genetic polymorphisms within the endothelin gene family have been implicated in the pathogenesis of atherosclerosis and hypertension.
Purpose of the Study:
- To investigate the association between ECE-1b gene polymorphisms (rs213045 and rs2038089) and the risk of developing coronary artery ectasia (CAE).
- To explore whether these ECE-1b polymorphisms are independent risk factors for CAE, considering other clinical factors like hypercholesterolemia and diabetes.
Main Methods:
- A case-control study involving 96 patients with CAE and 175 controls with normal coronary arteries.
- Genotyping of ECE-1b gene variations rs213045 (C>A or C338A) and rs2038089 (T>C) was performed using real-time polymerase chain reaction (PCR).
- Multivariate regression analysis was employed to assess the independent risk factors for CAE, including genetic polymorphisms and clinical conditions.
Main Results:
- The CC genotype of rs213045 and the T allele of rs2038089 were significantly more frequent in CAE patients compared to controls.
- Multivariate analysis identified the rs213045 CC genotype, rs2038089 T allele, and hypercholesterolemia as independent risk factors for CAE.
- In non-diabetic individuals, both ECE-1b polymorphisms were significant risk factors for CAE, whereas this association was not observed in diabetic subgroups.
Conclusions:
- ECE-1b gene polymorphisms (rs213045 and rs2038089) are associated with an increased risk of coronary artery ectasia.
- The risk conferred by these ECE-1b polymorphisms appears to be modulated by the presence of type II diabetes, suggesting a gene-environment interaction.
Abstract:
Coronary artery ectasia (CAE), defined as a 1.5-fold or greater enlargement of a coronary artery segment compared to the adjacent normal coronary artery, is frequently associated with atherosclerotic coronary artery disease (CAD). Membrane-bound endothelin converting enzyme-1 (ECE-1) is involved in the maturation process of the most potent vasoconstrictor ET-1. Polymorphisms in the endothelin (ET) gene family have been shown associated with the development of atherosclerosis. This study aims to investigate the effects of rs213045 and rs2038089 polymorphisms in the ECE-1 gene which have been previously shown to be associated with atherosclerosis and hypertension (HT), in CAE patients. Ninety-six CAE and 175 patients with normal coronary arteries were included in the study. ECE-1b gene variations rs213045 and rs2038089 were determined by real-time PCR. The frequencies of rs213045 C > A (C338A) CC genotype (60.4% vs. 35.4%, p < 0.001) and rs2038089 T > C T allele (64.58% vs. 35.42%, p = 0.017) were higher in the CAE group compared to the control group. The multivariate regression analysis showed that the ECE-1b rs213045 CC genotype (p = 0.001), rs2038089 T allele (p = 0.017), and hypercholesterolemia (HC) (p = 0.001) are risk factors for CAE. Moreover, in nondiabetic individuals of the CAE and control groups, it was observed that the rs213045 CC genotype (p < 0.001), and rs2038089 T allele (p = 0.003) were a risk factor for CAE, but this relationship was not found in the diabetic subgroups of the study groups (p > 0.05). These results show that ECE-1b polymorphisms may be associated with the risk of CAE and this relationship may change according to the presence of type II diabetes.
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