Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (2): 10-20.doi: 10.6040/j.issn.1671-7554.0.2024.0517

• Clinical Medicine • Previous Articles     Next Articles

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

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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

CLC Number: 

  • 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.
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