250例NSTE-ACS患者ACE、KLK1及PTGIS基因型联合相关性分析  

Correlation analysis of combining ACE,KLK1 and PTGIS genotypes among 250 NSTE-ACS patients

作　　者：侯晓慧 Arezou Bikdeli 马超[1] 李大庆[1] HOU Xiaohui;AREZOU Bikdeli;MA Chao;LI Daqing(State Key Laboratory for Innovation and Transformation of Luobing Theory,Key Laboratory of Cardiovascular Remodeling and Function Research,Ministry of Education,National Health Commission,Chinese Academy of Medical Sciences and Shandong Province,Department of Cardiology,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China)

机构地区：[1]络病理论创新转化国家重点实验室,教育部、国家卫健委、中国医学科学院和山东省心血管重构与功能研究重点实验室,山东大学齐鲁医院心内科,山东济南250012

出　　处：《山东大学学报(医学版)》2025年第2期10-20,共11页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金(26010132009125)。

摘　　要：目的探讨ACE插入(insertion,I)/缺失(deletion,D)、激肽释放酶基因(kallilrein gene,KLK)1(rs5517)、前列环素合成酶基因(prostacyclin synthase gene,PTGIS)(rs5629)基因位点多态性与250例非ST段抬高型急性冠状动脉综合征(non ST segment elevation acute coronary syndrome,NSTE-ACS)患者易感性及冠状动脉病变程度的关联。方法收集200例冠心病患者和50例同周期冠状动脉正常者的临床资料并分别通过PCR和Sanger测序进行基因分型。采用病例-对照分组,通过二分类Logistic回归分析与NSTE-ACS有关联的3个基因型及相互联合基因型的易感性。以Gensini评分和SYNTAX评分表示冠状动脉病变严重程度,采用多元线性回归分析相互联合基因型与冠状动脉病变严重程度的关联性。结果二元Logistic回归分析中,在调整年龄、LDL、同型半胱氨酸等混杂因素后,与NSTE-ACS危险性有关联的基因型为:ACE DD(OR=4.335,95%CI:1.105~17.016,P=0.036)、KLK1 CC(OR=3.152,95%CI:1.077~9.230,P=0.036)、KLK1 TT&PTGIS TT(OR=0.065,95%CI:0.006~0.752,P=0.029);多元线性回归分析中,与Gensini评分有关联的联合基因型为ACE DD&KLK1 CC(β=51.847,P=0.001),与SYNTAX评分有关联的联合基因型为ACE DD&KLK1 CC(β=10.031,P=0.001)。结论ACE I/D基因型和KLK1(rs5517)基因型与NSTE-ACS有关联,ACE DD基因型和KLK1 CC基因型增加NSTE-ACS的危险性;KLK1 TT&PTGIS TT亚型可能降低山东籍汉族人NSTE-ACS患病的危险性;ACE DD&KLK1 CC亚型与冠状动脉病变严重程度呈正向关联。Objective To investigate the association of ACE insertion/deletion,kallilrein gene(KLK)1(rs5517),prostacyclin synthase gene(PTGIS)(rs5629)locus polymorphisms with susceptibility and degree of coronary artery disease for 250 patients with non ST segment elevation acute coronary syndrome(NSTE-ACS).Methods Clinical data of 200 patients with coronary artery disease and 50 patients with normal coronary arteries were collected and genotyped by PCR and Sanger sequencing,respectively.Susceptibility of the three genotypes and mutual-combination genotypes associated with NSTE-ACS were analyzed by binary Logistic regression using case-control groupings.Gensini score and SYNTAX score were used to express the degree of coronary artery stenosis,and multiple linear regression was used to analyze the association between the mutual-combination genotypes and the severity of coronary artery disease.Results In binary Logistic regression analysis,after adjusting for confounding factors such as age,LDL,and homocysteine,the genotypes associated with the risk of NSTE-ACS were ACE DD(OR=4.335,95%CI:1.105-17.016,P=0.036),KLK1 CC(OR=3.152,95%CI:1.077-9.230,P=0.036),and KLK1 TT&PTGIS TT(OR=0.065,95%CI:0.006-0.752,P=0.029).In multiple linear regression analysis,the combined genotype associated with Gensini score was ACE DD&KLK1 CC(β=51.847,P=0.001),and the combined genotype associated with SYNTAX score was ACE DD&KLK1 CC(β=10.031,P=0.001).Conclusion ACE I/D genotype and KLK1(rs5517)genotype are associated with NSTE-ACS,and ACE DD genotype and KLK1 CC genotypes increase the risk of NSTE-ACS;KLK1 TT&PTGIS TT subtype may reduce the risk of NSTE-ACS patients of Han nationality in Shandong Province.ACE DD&KLK1 CC subtype is positively associated with the severity of coronary artery disease.

关 键 词：ACE插入/缺失 激肽释放酶基因1 前列环素合成酶基因 非ST段抬高型急性冠状动脉综合征 单核苷酸多态性 冠状动脉狭窄 

分 类 号：R541.4[医药卫生—心血管疾病]