乌兹别克斯坦人群杂合子家族性高胆固醇血症患者pcsk-9基因多态性e670g与颈动脉粥样硬化严重程度的相关性

R. Alieva, S. Hoshimov, S. S. Ahmedova, F. Bekmetova, A. Shek, R. Kurbanov
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The level of proprotein convertase subtilisin-kexin type 9 (PCSK-9) was measured with Human Proprotein Convertase 9/PCSK9 ELISA Kit (MULTI SCIENCE, China). The genetic typing of PCSK9 E670G (rs505151) polymorphism was performed by means of the PCR-RFLP method.Results. A comparison of the results of duplex scanning of carotid arteries in patients with HeFH showed that the carotid intima-media thickness (CIMT) on the left (1.14±0.18 mm, P<0.01) and on the right (1.15±0.16 mm, P<0.01) was higher, than in the comparison group: 1.05±0.17 mm and 1.04±0.18 mm, respectively. The studies revealed a positive correlation between the incidence of Myocardial infarction (MI) in the history in patients with HeFH and the (r=0.38, P<0.05). The CIMT also correlated with an increase in the concentration of PCSK9 (r = 0.31, P <0.05) in the blood and the carriage of the G allele of polymorphism E670G (r = 0.39, P <0.05) of the PCSK9 gene.Conclusion. 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引用次数: 0

摘要

目的:研究乌兹别克斯坦人群杂合子家族性高胆固醇血症患者颈动脉粥样硬化的严重程度与PCSK-9水平及PCSK-9基因遗传多态性E670G的关系。材料和方法。本研究纳入57例慢性稳定型冠状动脉疾病(SCAD)合并家族性杂合型高胆固醇血症(HeFH, I组)患者,对照组144例无HeFH的SCAD患者分为两组:A组研究前未使用他汀类药物(n=63), B组作为门诊患者使用他汀类药物(n=81);对照组由17名健康人组成。采用Human proprotein convertase 9/PCSK9 ELISA Kit (MULTI SCIENCE, China)检测蛋白转化酶枯草素-激酶9 (PCSK-9)水平。采用PCR-RFLP方法对PCSK9 E670G (rs505151)多态性进行遗传分型。对比HeFH患者颈动脉双相扫描结果显示,左侧颈动脉内膜-中膜厚度(CIMT)(1.14±0.18 mm, P<0.01)和右侧颈动脉内膜-中膜厚度(CIMT)(1.15±0.16 mm, P<0.01)高于对照组(1.05±0.17 mm和1.04±0.18 mm)。研究发现,HeFH患者史上心肌梗死(MI)的发生率与心绞痛的发生率呈正相关(r=0.38, P<0.05)。CIMT与PCSK9血中浓度升高(r = 0.31, P <0.05)和PCSK9基因E670G多态性等位基因携带(r = 0.39, P <0.05)相关。在乌兹别克斯坦人群中患有杂合子家族性高胆固醇血症的住院患者中,心肌梗死史、颈动脉内膜-中膜厚度、血液中PCSK-9浓度的增加和PCSK9基因E670G多态性的G等位基因的携带之间建立了直接相关性,这使得它们可以用作心血管并发症发生风险的预后标志物。
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ASSOTIATION OF THE GENETIC POLYMORPHISM E670G OF THE PCSK-9 AND THE SEVERITY OF THE CAROTID ATHEROSCLEROSIS IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IN UZBEK POPULATION
Objective: to study the severity of carotid artery atherosclerosis in patients with heterozygous familial hypercholesterolemia in the Uzbek population, depending on the level of PCSK-9 and the genetic polymorphism E670G of the PCSK-9 gene.Material and methods. The study included 57 patients with chronic stable coronary artery disease (SCAD) and familial heterozygous hypercholesterolemia (HeFH, group I). The comparison group consisted of 144 patients with SCAD without HeFH divided into two subgroups: A - statin free before the research (n=63) and B (n=81) who took it as outpatients; control group consisted of 17 healthy people. The level of proprotein convertase subtilisin-kexin type 9 (PCSK-9) was measured with Human Proprotein Convertase 9/PCSK9 ELISA Kit (MULTI SCIENCE, China). The genetic typing of PCSK9 E670G (rs505151) polymorphism was performed by means of the PCR-RFLP method.Results. A comparison of the results of duplex scanning of carotid arteries in patients with HeFH showed that the carotid intima-media thickness (CIMT) on the left (1.14±0.18 mm, P<0.01) and on the right (1.15±0.16 mm, P<0.01) was higher, than in the comparison group: 1.05±0.17 mm and 1.04±0.18 mm, respectively. The studies revealed a positive correlation between the incidence of Myocardial infarction (MI) in the history in patients with HeFH and the (r=0.38, P<0.05). The CIMT also correlated with an increase in the concentration of PCSK9 (r = 0.31, P <0.05) in the blood and the carriage of the G allele of polymorphism E670G (r = 0.39, P <0.05) of the PCSK9 gene.Conclusion. Inpatientswithheterozygousfamilialhypercholesterolemia in the Uzbek population a direct correlation was established between Myocardial infarction in the history, the carotid intima-media thickness, an increase in the concentration of PCSK-9 in the blood and the carriage of the G allele of E670G polymorphism of the PCSK9 gene, that allows them to be used as prognostic markers for the risk of development of cardiovascular complications.
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