冠心病患者外周血人枯草溶菌素转化酶9基因V312F位点的多态性及其临床意义
Polymorphism of V312F locus in PCSK9 gene of patients with coronary heart disease and its clinical significance

摘要：目的 探讨外周血人枯草溶菌素转化酶9(PCSK9)基因V312F多态性与不同类型冠心病之间的关系及临床意义。方法 选取2014年1月-2016年1月年在我院就诊的不同类型冠心病患者3560例作为病例组，按照解剖及病理生理变化分为心绞痛、心肌梗死、无症状心肌缺血、缺血性心肌病、猝死5组，同期健康体检者1000例为对照组。应用聚合酶链反应(PCR)结合DNA直接测序技术，对所有入选者PCSK9基因V312F(T/G)多态位点进行分型。多因素Logistic回归分析PCSK9基因V312F多态位点与不同类型冠心病的相关性。同时检测研究对象的血脂及PCSK9水平。结果 病例组血清PCSK9、TC、TG、LDLC、阳性家族史的比例高于对照组，HDLC低于对照组(均P<0.05)；病例组中猝死组各指标变化最明显，无症状心肌缺血组变化最小。病例组中TT、GT基因型和T等位基因频率分别为3.4%、16.6%和11.7%，明显高于对照组(1.1%、10.2%、6.2%)(P均<0.01)。病例组中猝死组TT、GT的基因型频率、T等位基因频率最高，无症状心肌缺血组最低(P<0.05)。Logistic回归分析发现PCSK9基因V312F(T/G)多态位点TT基因型与冠心病的严重程度有关(OR值为8.463，95% CI为3.505～17.854，P<0.001)。结论 PCSK9基因V312F(T/G)位点基因突变与冠心病严重程度有关。
ABSTRACT: Objective To explore the correlation and significance of V312F locus polymorphism of PCSK9 gene in patients with coronary heart disease. Methods We selected 3560 patients with coronary heart disease who came to our hospital from January 2014 to January 2016 as the case group. They were divided into 5 subgroups: angina group, myocardial infarction group, silent myocardial ischemia group, ischemic cardiomyopathy group, and sudden death group, according to their anatomic and pathophysiological features. Data of 1000 people for physical examination served as the control group. PCR assay combined with direct sequencing method was applied to test V312F locus polymorphism of PCSK9 gene. Logistic regression analysis was used to analyze relationship between V312F locus polymorphism of PCSK9 gene and types of coronary heart disease. The concentration of serum PCSK9 and lipids of the two groups were also measured. Results The serum levels of PCSK9, TC, TG and LDLC and ratio of positive family history in the case group were significantly higher than those in the control group, while the level of HDLC was lower than that of the controls (all P<0.05). Indexes of sudden death subgroup in the case group showed the most significant changes, while asymptomatic myocardial ischemia subgroup showed the weakest changes. The frequency of genotype TT, GT and allele T in the case group was 3.4%, 16.6% and 11.7%, respectively, which was significantly higher than that in the control group (1.1%, 10.2% and 6.2%) (all P<0.01). The highest frequency of genotype TT, GT and allele T was found in sudden death subgroup, and the lowest frequency of these indexes was found in asymptomatic myocardial ischemia subgroup (P<0.05). Results of Logistic regression analysis showed that genotype TT in V312F locus of PCSK9 gene was related to the severity of coronary heart disease (OR=8.463, 95% CI from 3.505 to 17.854, P<0.001).Conclusion The