RESUMEN

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.

RESUMEN

Recent reports showing that neo-atherosclerosis formation in stented coronary artery is characterized by the accumulation of lipid-laden macrophages within the neointima has strengthened the possibility that elevated low-density lipoprotein (LDL)-cholesterol may be a risk factor for in-stent restenosis (ISR). Protein Convertase Subtilisin/Kexin-9 (PCSK9) protein plays an important role in cholesterol metabolism by degrading of LDL receptors. The gain-of-function E670G (rs505151) mutation of the PCSK9 gene is a well-known genetic risk factor for hypercholesterolemia. This study evaluated for the first time the association of the E670G variation with the serum lipids, PCSK9 levels and concomitant diseases on the ISR risk. The study included 109 ISR, and 82 Non-ISR patients, based on the results of coronary angiography. Genotypes were determined using the real-time PCR and serum PCSK9 levels were measured by ELISA technique. The rare G allele of PCSK9 E670G (p < 0.05), hyperlipidemia (HL) (p < 0.001), and type 2 diabetes (T2DM) (p < 0.01) were associated with increased risk for ISR. In hyperlipidemic conditions, the E670G-G allele was associated with hypercholesterolemia and a higher risk of ISR (p < 0.001), while the E670G-AA genotype has been associated with a high prevalence of T2DM and hypertension. In addition, diabetic ISRs had higher serum PCSK9 levels (p < 0.05) and the E670G-AA genotype was associated with increased levels of diabetes markers. Our results indicated that the unusual effects of both G allele and AA genotype of the PCSK9 E670G variation may be involved in the risk of ISR in association with concomitant metabolic diseases.

This study evaluated the association of the Protein Convertase Subtilisin/Kexin-9 (PCSK9) E670G mutation with the serum lipids, PCSK9 levels and concomitant diseases on the in-stent restenosis (ISR) risk. The E670G-G allele, hyperlipidemia, and type 2 diabetes (T2DM) were found risk factors for ISR. In hyperlipidemic conditions, the E670G-G allele was associated with hypercholesterolemia and a higher risk of ISR, while the E670G-AA genotype has been associated with a high prevalence of T2DM and hypertension. Our results indicated that the unusual effects of both genotypes of the E670G that may be involved in the ISR risk in association with concomitant diseases.