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  • 张明明,赵培,于悦卿,张翠改,高伟,李芳.冠心病患者PCSK9基因D320N位点多态性及其临床意义[J].第二军医大学学报,2018,39(3):291-296    [点击复制]
  • ZHANG Ming-ming,ZHAO Pei,YU Yue-qing,ZHANG Cui-gai,GAO Wei,LI Fang.Polymorphism of D320N locus in PCSK9 gene of patients with coronary heart disease and its clinical significance[J].Acad J Sec Mil Med Univ,2018,39(3):291-296   [点击复制]
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冠心病患者PCSK9基因D320N位点多态性及其临床意义
张明明1*,赵培1,于悦卿1,张翠改2,高伟1,李芳3
0
(1. 河北省人民医院检验科, 石家庄 050051;
2. 河北省人民医院体检中心, 石家庄 050051;
3. 河北省人民医院风湿免疫科, 石家庄 050051
*通信作者)
摘要:
目的 探讨外周血人枯草溶菌素转化酶9(PCSK9)基因D320N多态性与冠心病的关系。方法 选取2014年1月至2016年1月在河北省人民医院就诊的不同类型(心绞痛、心肌梗死、无症状性心肌缺血、缺血性心肌病、猝死)冠心病患者3 450例为病例组,以同期1 100名健康体检人群为对照组。检测各组研究对象的血清血脂水平及PCSK9浓度。应用PCR结合DNA直接测序技术对各组PCSK9基因D320N(A/G)多态位点进行分型。采用多因素logistic回归分析PCSK9基因D320N多态位点与不同类型冠心病的关系。结果 病例组患者血清PCSK9浓度、总胆固醇水平、三酰甘油水平、低密度脂蛋白胆固醇水平、冠心病家族史者所占比例和吸烟率均高于对照组(P<0.001),高密度脂蛋白胆固醇水平低于对照组(P<0.001)。病例组中AA、GA的基因型频率分别为3.6%、13.9%,分别高于对照组的1.1%、7.0%(χ2=20.502、39.646,P<0.001);病例组中A等位基因的频率为10.5%,高于对照组的4.6%(χ2=70.481,P<0.001)。病例组中猝死组AA、GA的基因型频率和A等位基因频率最高,无症状性心肌缺血组最低。Logistic回归分析发现PCSK9基因D320N(A/G)多态位点GA、AA基因型为冠心病的独立危险因素(P均<0.001)。结论 PCSK9基因D320N(A/G)位点基因突变与冠心病有关,其中AA基因型可能是冠心病发生的独立危险因素。
关键词:  前蛋白转化酶枯草杆菌蛋白酶kexin 9型  基因多态性  冠状动脉粥样硬化性心脏病  脂质
DOI:10.16781/j.0258-879x.2018.03.0291
投稿时间:2017-08-12修订日期:2017-12-19
基金项目:河北省科技支撑项目(16277771D).
Polymorphism of D320N locus in PCSK9 gene of patients with coronary heart disease and its clinical significance
ZHANG Ming-ming1*,ZHAO Pei1,YU Yue-qing1,ZHANG Cui-gai2,GAO Wei1,LI Fang3
(1. Department of Clinical Laboratory, Hebei General Hospital, Shijiazhuang 050051, Hebei, China;
2. Physical Examination Center, Hebei General Hospital, Shijiazhuang 050051, Hebei, China;
3. Department of Rheumatic Immunology, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
*Corresponding author)
Abstract:
Objective To explore the relationship between D320N locus polymorphism in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and coronary heart disease. Methods A total of 3 450 patients with coronary heart diseases (angina pectoris, myocardial infarction, asymptomatic myocardial ischemia, ischemic cardiomyopathy, and sudden death), who were treated in Hebei General Hospital from Jan. 2014 to Jan. 2016, were enrolled as the case group, with 1 100 healthy people in the same period served as controls. Serum lipid levels and PCSK9 concentrations of subjects in the two groups were detected. PCR assay combined with DNA direct sequencing method was applied in genotyping of D320N (A/G) polymorphic locus in PCSK9 gene. Logistic regression analysis was used to analyze the relationship between D320N locus polymorphism in PCSK9 gene and different types of coronary heart diseases. Results Serum concentrations of PCSK9, levels of total cholesterol, triacylglycerol and low density lipoprotein cholesterol, ratio of coronary heart disease family, and ratio of smoking of subjects in the case group were significantly higher than those in the control group (P<0.001), while the level of high density lipoprotein cholesterol was significantly lower than that in the control group (P<0.001). The frequencies of genotype AA and GA in the case group were 3.6% and 13.9%, respectively, which were significantly higher than those in the control group, respectively (1.1%, 7.0%; χ2=20.502, 39.646; P<0.001); the frequency of allele A in the case group was significantly higher than that in the control group (10.5% vs 4.6%, χ2=70.481, P<0.001). The frequencies of genotype AA, genotype GA and allele A were the highest in the sudden death group, and were the lowest in the asymptomatic myocardial ischemia group. Logistic regression analysis showed that genotypes AA and GA of D320N (A/G) polymorphic in PCSK9 gene were risk factors of coronary heart disease (both P<0.001). Conclusion The D320N (A/G) locus polymorphism in PCSK9 gene was associated with coronary heart disease, and genotype AA may be an independent risk factor of coronary heart disease.
Key words:  proprotein convertase subtilisin/kexin type 9  gene polymorphism  coronary atherosclerotic heart disease  lipid