您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (2): 10-20.doi: 10.6040/j.issn.1671-7554.0.2024.0517

• 临床医学 • 上一篇    下一篇

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

侯晓慧,Arezou Bikdeli,马超,李大庆   

  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
  • 出版日期:2025-03-10 发布日期:2025-03-07
  • 通讯作者: 李大庆. E-mail:daqingli999@163.com
  • 基金资助:
    山东省自然科学基金(26010132009125)

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

HOU Xiaohui, AREZOU Bikdeli, MA Chao, LI Daqing   

  1. 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
  • Online:2025-03-10 Published:2025-03-07

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。

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

Abstract: 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.

Key words: ACE insertion/deletion, Kallilrein gene 1, Prostacyclin synthase gene, Non ST segment elevation acute coronary syndrome, Single nucleotide polymorphism, Coronary artery stenosis

中图分类号: 

  • R541.4
[1] Mocan O, Radulescu D, Buzdugan E, et al. Association between M235T-AGT and I/D-ACE polymorphisms and carotid atheromatosis in hypertensive patients: a cross-sectional study[J]. In Vivo, 2020, 34(5): 2811-2819.
[2] Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines[J]. J Am Coll Cardiol, 2014, 64(24): e139-e228.
[3] Ghazali H, Gammoudi M, Yahmadi A, et al. Acute coronary syndrome without persistent ST segment elevation in the emergency department: epidemiology, clinical features and prognosis[J]. Tunis Med, 2017, 95(12): 229-235.
[4] Liu RF, Xu FX, Zhou YJ, et al. The characteristics of risk factors in Chinese young women with acute coronary syndrome[J]. BMC Cardiovasc Disord, 2020, 20(1): 290. doi:10.1186/s12872-020-01577-z.
[5] Sanchis-Gomar F, Perez-Quilis C, Leischik R, et al. Epidemiology of coronary heart disease and acute coronary syndrome[J]. Ann Transl Med, 2016, 4(13): 256. doi:10.21037/atm.2016.06.33.
[6] Khera AV, Kathiresan S. Genetics of coronary artery disease: discovery, biology and clinical translation[J]. Nat Rev Genet, 2017, 18(6): 331-344.
[7] Tian JW, Hu SY, Wang F, et al. PPARG, AGTR1, CXCL16 and LGALS2 polymorphisms are correlated with the risk for coronary heart disease[J]. Int J Clin Exp Pathol, 2015, 8(3): 3138-3143.
[8] Nouryazdan N, Adibhesami G, Birjandi M, et al. Study of angiotensin-converting enzyme insertion/deletion polymorphism, enzyme activity and oxidized low density lipoprotein in Western Iranians with atherosclerosis: a case-control study[J]. BMC Cardiovasc Disord, 2019, 19(1): 184. doi:10.1186/S12872-019-1158-4.
[9] Tran DC, Le LHG, Thai TT, et al. Association between ACE I/D genetic polymorphism and the severity of coronary artery disease in Vietnamese patients with acute myocardial infarction[J]. Front Cardiovasc Med, 2023, 10: 1091612. doi:10.3389/fcvm.2023.1091612.
[10] da Silva GA, Atum ALB, de Matos LP, et al. Sexual dimorphism in the expression of cardiac and hippocampal renin-angiotensin and kallikrein-kinin systems in offspring from mice exposed to alcohol during gestation[J]. Antioxidants, 2023, 12(3): 541. doi:10.3390/antiox12030541.
[11] Nakayama T, Soma M, Saito S, et al. Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction[J]. Am Heart J, 2002, 143(5): 797-801.
[12] Lemaitre RN, Rice K, Marciante K, et al. Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke[J]. Atherosclerosis, 2009, 204(2): e58-e63.
[13] Zhang YJ, Yang T, Zhou WJ, et al. A meta-analysis on the association of genetic polymorphism of the angiotensin-converting enzyme and coronary artery disease in the Chinese population[J]. Rev Assoc Med Bras, 2019, 65(6): 923-929.
[14] Gao M, Tang HQ, Zheng XD, et al. Association analysis of GWAS and candidate gene loci in a Chinese population with coronary heart disease[J]. Int J Clin Exp Med, 2015, 8(5): 7497-7506.
[15] Hara M, Sakata Y, Nakatani D, et al. Renin-angiotensin-aldosterone system polymorphisms and 5-year mortality in survivors of acute myocardial infarction: a report from the Osaka Acute Coronary Insufficiency Study [J]. Int Heart J, 2014, 55(3): 190-196.
[16] Dai SH, Li JF, Feng JB, et al. Association of serum levels of AngII, KLK1, and ACE/KLK1 polymorphisms with acute myocardial infarction induced by coronary artery stenosis[J]. J Renin Angiotensin Aldosterone Syst, 2016, 17(2): 1470320316655037. doi:10.1177/1470320316655037.
[17] 张静. RAS基因多态性与肥胖相关性的研究进展[J]. 海南医学, 2023, 34(6): 889-893. ZHANG Jing. Research progress on the correlation between RAS gene polymorphism and obesity[J]. Hainan Medical Journal, 2023, 34(6): 889-893.
[18] Sahin S, Ceyhan K, Benli I, et al. Traditional risk factors and angiotensin-converting enzyme insertion/deletion gene polymorphism in coronary artery disease[J]. Genet Mol Res, 2015, 14(1): 2063-2068.
[19] Susilo H, Pikir BS, Thaha M, et al. The effect of angiotensin converting enzyme(ACE)I/D polymorphism on atherosclerotic cardiovascular disease and cardiovascular mortality risk in non-hemodialyzed chronic kidney disease: the mediating role of plasma ACE level[J]. Genes, 2022, 13(7): 1121. doi:10.3390/genes13071121.
[20] Dai SH, Ding M, Liang N, et al. Associations of ACE I/D polymorphism with the levels of ACE, kallikrein, angiotensin II and interleukin-6 in STEMI patients[J]. Sci Rep, 2019, 9(1): 19719. doi:10.1038/s41598-019-56263-8.
[21] Moorthy N, Saligrama Ramegowda K, Jain S, et al. Role of Angiotensin-Converting Enzyme(ACE)gene polymorphism and ACE activity in predicting outcome after acute myocardial infarction[J]. Int J Cardiol Heart Vasc, 2021, 32: 100701. doi:10.1016/j.ijcha.2020.100701.
[22] Fu SS, Li FJ, Wang YY, et al. Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression[J]. PLoS One, 2013, 8(9): e73035. doi:10.1371/journal.pone.0073035.
[23] Zhang Q, Ran X, Wang DW. Relation of plasma tissue kallikrein levels to presence and severity of coronary artery disease in a Chinese population[J]. PLoS One, 2014, 9(3): e91780. doi:10.1371/journal.pone.0091780.
[24] 吴永茂, 李泽荣, 朱深政. 血清KLK1、RBP4及SYNTAX-11评分预测血运重建后STEMI患者预后的临床价值[J]. 中国急救复苏与灾害医学杂志, 2022, 17(2): 217-220. WU Yongmao, LI Zerong, ZHU Shenzheng. Clinical value of serum KLK1 and RBP4 and SYNTAX-11 score in predicting the prognosis of STEMI after revascularization [J]. China Journal of Emergency Resuscitation and Disaster Medicine, 2022, 17(2): 217-220.
[25] Xiang X, Ma YT, Fu ZY, et al. Haplotype analysis of the CYP8A1 gene associated with myocardial infarction[J]. Clin Appl Thromb Hemost, 2009, 15(5): 574-580.
[1] 葛丽娟 金瑞峰 王纪文 许新升 李癊. 多药耐药基因1 C1236T多态性与癫痫患者对药物反应性的相关性[J]. 山东大学学报(医学版), 2209, 47(6): 99-102.
[2] 高青,鲁婷,单珊,陶靖,金华. 364例孕早中期自然流产组织单核苷酸多态性微阵列分析[J]. 山东大学学报 (医学版), 2022, 60(10): 68-73.
[3] 孟朝暾,李钦, 孙卉,邬信芳,孙文凯,高伟. 白细胞介素18单核苷酸多态性与73例喉鳞状细胞癌易感性的关联性[J]. 山东大学学报 (医学版), 2020, 1(9): 58-63.
[4] 杜金阁,陈慧,杨孝荣,吕明. STAT4 rs7574865位点单核苷酸多态性与系统性红斑狼疮易感性Meta分析[J]. 山东大学学报(医学版), 2017, 55(5): 95-102.
[5] 白杨1,崔国忠1,戴殿禄1,桑梅香2,耿翠芝3. Bax基因多态性与乳腺癌临床病理特点的关系[J]. 山东大学学报(医学版), 2014, 52(1): 71-74.
[6] 严倩1,鲁衍强2,李瑛2,石春红1,姜凌1,于传亭1. 烟台市汉族女性MTHFR和MTRR基因多态性的分布特征[J]. 山东大学学报(医学版), 2014, 52(1): 79-84.
[7] 习海波,傅龙龙,王共先,傅斌,李煜,宋小芬. 尿激酶3′-UTR 基因多态性与特发性草酸钙结石易感性的关系[J]. 山东大学学报(医学版), 2013, 51(5): 105-107.
[8] 臧静1,张涌2,王滨2,杨绍祥2,李彬2,王建丽1. CD36单核苷酸多态性与老年动脉粥样硬化性脑梗死的相关性[J]. 山东大学学报(医学版), 2013, 51(5): 99-104.
[9] 廖小莉1,谢伟敏2,胡晓桦1,李永强1,刘志辉1,陆永奎2,王洪学2. 着色性干皮病基因D Lys751Gln多态性与非霍奇金淋巴瘤临床表型及化疗疗效的相关性[J]. 山东大学学报(医学版), 2013, 51(4): 62-66.
[10] 孙瑾,韩波,魏美丽,杨文巍,王介忠,刘永蛟. 动脉导管未闭患儿TFAP2B基因变异筛查[J]. 山东大学学报(医学版), 2013, 51(3): 72-75.
[11] 刘晨帆1,王震英2,宋怀东3,潘春明3,张莉2. 浅表播散型汗孔角化症致病候选基因的突变筛查[J]. 山东大学学报(医学版), 2013, 51(1): 93-97.
[12] 周忠伟1,杨雄1,万应彪2,信燕华1,翟堃1,马坚2,黄永清2,姜敏3,王怡瑞4. 宁夏回汉族人群中染色体17q22、10q25.3和ABCA4基因多态性与非综合征型唇腭裂的关联[J]. 山东大学学报(医学版), 2013, 51(1): 103-108.
[13] 陈静1,耿厚法2,孙琳2. FTO rs9939609多态性与2型糖尿病合并冠心病的相关性[J]. 山东大学学报(医学版), 2012, 50(7): 10-.
[14] 孙亚方1,王银昌2,王来城3,焦玉莲3,崔彬3,夏羽3,卢冰如3,赵跃然1,3. 一个Paget骨病家系SQSTM1及TNFRSF11A基因突变分析[J]. 山东大学学报(医学版), 2012, 50(12): 107-113.
[15] 张凌云1,2,赵家军1,金勇君2,李建周2 . 2型糖尿病患者抵抗素基因420 C/G多态性与非酒精性脂肪肝的关系[J]. 山东大学学报(医学版), 2011, 49(7): 1-5.
Viewed
Full text
28
HTML PDF
Just accepted Online first Issue Just accepted Online first Issue
0 0 0 0 0 28

  From Others local
  Times 1 27
  Rate 4% 96%

Abstract
58
Just accepted Online first Issue
0 0 58
  From Others
  Times 58
  Rate 100%

Cited

Web of Science  Crossref   ScienceDirect  Search for Citations in Google Scholar >>
 
This page requires you have already subscribed to WoS.
  Shared   
  Discussed   
No Suggested Reading articles found!