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Published in: BMC Cardiovascular Disorders 1/2019

Open Access 01-12-2019 | Clopidogrel | Research article

Relationship between ALDH2 genotype and in-stent restenosis in Chinese Han patients after percutaneous coronary intervention

Authors: Lizhi Lv, Weijie Ye, Peiyuan Song, Yubin Chen, Jing Yang, Congmin Zhang, Xiaoping Chen, Fanyan Luo

Published in: BMC Cardiovascular Disorders | Issue 1/2019

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Abstract

Background

It is well known that the genotype of ALDH2 is associated with coronary artery disease (CAD), and in-stent restenosis (ISR) is a primary complication of percutaneous coronary intervention (PCI), a primary recommended treatment for CAD. The aim of this study was to identify the relationship between aldehyde dehydrogenase 2 (ALDH2) genotype and in-stent restenosis (ISR).

Methods

This study recruited 531 patients who were undergoing PCI at two Chinese hospitals from 2015 to 2017 and 183 were diagnosed with ISR after PCI during the one-year follow-up period. We used polymerase chain restriction fragment length polymorphism (PCR-RFLP) and sequencing to determine ALDH2 polymorphisms.

Results

Among all 531 patients (mean age = 59.4 ± 9.8; 65.9% male), 68.7% carried the wild-type genotype, 28.4% were heterozygous for the mutation, and 2.8% were homozygous for the mutation. Multiple logistical regression analyses indicated no correlation between ALDH2 genotype and the occurrence of restenosis after PCI (OR = 1.448, 95% CI: 0.965–2.168, p = 0.073), though a significant association was observed for patients with diabetes (OR = 4.053, 95% CI: 1.668–10.449, p = 0.003).

Conclusion

In this study, we found that carrying an ALDH2*2 allele had no notable relationship with ISR one year after PCI but that it did have a significant association with complications in diabetic patients. Further studies with larger sample sizes will be necessary to reveal a consensus.
Appendix
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Literature
1.
go back to reference Members ATF, Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, Di Mario C, Dickstein K, Ducrocq G. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J. 2012;33(20):2569–619.CrossRef Members ATF, Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, Di Mario C, Dickstein K, Ducrocq G. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J. 2012;33(20):2569–619.CrossRef
2.
go back to reference Pang J, Wang J, Zhang Y, Xu F, Chen Y. Targeting acetaldehyde dehydrogenase 2 (ALDH2) in heart failure—recent insights and perspectives. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2017;1863(8):1933–41.CrossRef Pang J, Wang J, Zhang Y, Xu F, Chen Y. Targeting acetaldehyde dehydrogenase 2 (ALDH2) in heart failure—recent insights and perspectives. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2017;1863(8):1933–41.CrossRef
3.
go back to reference Weintraub WS, Grau-Sepulveda MV, Weiss JM, DeLong ER, Peterson ED, O'brien SM, Kolm P, Klein LW, Shaw RE, McKay C. Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry. Circulation. 2012;125(12):1501–10.CrossRef Weintraub WS, Grau-Sepulveda MV, Weiss JM, DeLong ER, Peterson ED, O'brien SM, Kolm P, Klein LW, Shaw RE, McKay C. Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry. Circulation. 2012;125(12):1501–10.CrossRef
4.
go back to reference Huang Y, Salu K, Wang L, Liu X, Li S, Lorenz G, Wnendt S, Verbeken E, Bosmans J, dWF V. Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine coronary model. J Invasive Cardiol. 2005;17(3):142.PubMed Huang Y, Salu K, Wang L, Liu X, Li S, Lorenz G, Wnendt S, Verbeken E, Bosmans J, dWF V. Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine coronary model. J Invasive Cardiol. 2005;17(3):142.PubMed
5.
go back to reference Pleva L, Kusnierova P, Plevova P, Zapletalova J, Karpisek M, Faldynova L, Kovarova P, Kukla P. Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159(4):586–94.CrossRef Pleva L, Kusnierova P, Plevova P, Zapletalova J, Karpisek M, Faldynova L, Kovarova P, Kukla P. Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159(4):586–94.CrossRef
6.
go back to reference Wang R-S, Nakajima T, Kawamoto T, Honma T. Effects of aldehyde dehydrogenase-2 genetic polymorphisms on metabolism of structurally different aldehydes in human liver. Drug Metab Dispos. 2002;30(1):69–73.CrossRef Wang R-S, Nakajima T, Kawamoto T, Honma T. Effects of aldehyde dehydrogenase-2 genetic polymorphisms on metabolism of structurally different aldehydes in human liver. Drug Metab Dispos. 2002;30(1):69–73.CrossRef
7.
go back to reference Wenzel P, Schuhmacher S, Kienhöfer J, Müller J, Hortmann M, Oelze M, Schulz E, Treiber N, Kawamoto T, Scharffetter-Kochanek K. Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction. Cardiovasc Res. 2008;80(2):280–9.CrossRef Wenzel P, Schuhmacher S, Kienhöfer J, Müller J, Hortmann M, Oelze M, Schulz E, Treiber N, Kawamoto T, Scharffetter-Kochanek K. Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction. Cardiovasc Res. 2008;80(2):280–9.CrossRef
9.
go back to reference Peng L-M, Chen X-P, Sun J, Guo Y-J, Li L, Mo L, Xie W, Li Y-J, Yang T-L, Li C-C. Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of calcitonin gene related peptide (CGRP). Int J Clin Pharmacol Ther. 2012;50(10):701–11.CrossRef Peng L-M, Chen X-P, Sun J, Guo Y-J, Li L, Mo L, Xie W, Li Y-J, Yang T-L, Li C-C. Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of calcitonin gene related peptide (CGRP). Int J Clin Pharmacol Ther. 2012;50(10):701–11.CrossRef
11.
go back to reference Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, Pichard AD, Kent KM, Stone GW, Leon MB. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation. 1999;100(18):1872–8.CrossRef Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, Pichard AD, Kent KM, Stone GW, Leon MB. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation. 1999;100(18):1872–8.CrossRef
12.
go back to reference Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2013;22(4):193–278.CrossRef Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2013;22(4):193–278.CrossRef
13.
go back to reference Expert Panel on Detection E. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). Jama. 2001;285(19):2486.CrossRef Expert Panel on Detection E. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). Jama. 2001;285(19):2486.CrossRef
14.
go back to reference Idiopathic B, Endocrinopathies D. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26:S5–S20.CrossRef Idiopathic B, Endocrinopathies D. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26:S5–S20.CrossRef
15.
go back to reference Guo Y-J, Chen L, Bai Y-P, Li L, Sun J, Zhang G-G, Yang T-L, Xia J, Li Y-J, Chen X-P. The ALDH2 Glu504Lys polymorphism is associated with coronary artery disease in Han Chinese: relation with endothelial ADMA levels. Atherosclerosis. 2010;211(2):545–50.CrossRef Guo Y-J, Chen L, Bai Y-P, Li L, Sun J, Zhang G-G, Yang T-L, Xia J, Li Y-J, Chen X-P. The ALDH2 Glu504Lys polymorphism is associated with coronary artery disease in Han Chinese: relation with endothelial ADMA levels. Atherosclerosis. 2010;211(2):545–50.CrossRef
16.
go back to reference Shen Y, Li C, Zhang RY, Zhang Q, Shen WF, Ding FH, Lu L. Association of increased serum CTRP5 levels with in-stent restenosis after coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration and proliferation in vascular smooth muscle cells. Int J Cardiol. 2017;228:129–36.CrossRef Shen Y, Li C, Zhang RY, Zhang Q, Shen WF, Ding FH, Lu L. Association of increased serum CTRP5 levels with in-stent restenosis after coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration and proliferation in vascular smooth muscle cells. Int J Cardiol. 2017;228:129–36.CrossRef
17.
go back to reference Ma W, Liang Y, Zhu J, Chen T, Feng G, Yang Y, Liu X, Wang X. Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting. Atherosclerosis. 2016;251:305–10.CrossRef Ma W, Liang Y, Zhu J, Chen T, Feng G, Yang Y, Liu X, Wang X. Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting. Atherosclerosis. 2016;251:305–10.CrossRef
18.
go back to reference Zhang R, Wang J, Xue M, Xu F, Chen Y. ALDH2---the genetic polymorphism and enzymatic activity regulation: their epidemiologic and clinical implications. Curr Drug Targets. 2015;18(15):1810–6. Zhang R, Wang J, Xue M, Xu F, Chen Y. ALDH2---the genetic polymorphism and enzymatic activity regulation: their epidemiologic and clinical implications. Curr Drug Targets. 2015;18(15):1810–6.
19.
go back to reference Yavari A, Ashrafian H. Potentiating mitochondrial aldehyde dehydrogenase 2 to treat post-infarction heart failure. Cardiovasc Res. 2014;103(4):429.CrossRef Yavari A, Ashrafian H. Potentiating mitochondrial aldehyde dehydrogenase 2 to treat post-infarction heart failure. Cardiovasc Res. 2014;103(4):429.CrossRef
20.
go back to reference Wenzel P, Müller J, Zurmeyer S, Schuhmacher S, Schulz E, Oelze M, Pautz A, Kawamoto T, Wojnowski L, Kleinert H. ALDH-2 deficiency increases cardiovascular oxidative stress---evidence for indirect antioxidative properties. Biochem Biophys Res Commun. 2008;367(1):137–43.CrossRef Wenzel P, Müller J, Zurmeyer S, Schuhmacher S, Schulz E, Oelze M, Pautz A, Kawamoto T, Wojnowski L, Kleinert H. ALDH-2 deficiency increases cardiovascular oxidative stress---evidence for indirect antioxidative properties. Biochem Biophys Res Commun. 2008;367(1):137–43.CrossRef
21.
go back to reference Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J, Davidson CJ, McKoy JM, Raisch DW, Whisenant BK. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the research on adverse drug events and reports (RADAR) project. J Am Coll Cardiol. 2006;47(1):175–81.CrossRef Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J, Davidson CJ, McKoy JM, Raisch DW, Whisenant BK. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the research on adverse drug events and reports (RADAR) project. J Am Coll Cardiol. 2006;47(1):175–81.CrossRef
22.
go back to reference Churchill EN, Disatnik M-H, Mochly-Rosen D. Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of ɛPKC and activation of aldehyde dehydrogenase 2. J Mol Cell Cardiol. 2009;46(2):278–84.CrossRef Churchill EN, Disatnik M-H, Mochly-Rosen D. Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of ɛPKC and activation of aldehyde dehydrogenase 2. J Mol Cell Cardiol. 2009;46(2):278–84.CrossRef
23.
go back to reference Yang H, Song Z, Yang G-P, Zhang B-K, Chen M, Wu T, Guo R. The ALDH2 rs671 polymorphism affects post-stroke epilepsy susceptibility and plasma 4-HNE levels. PLoS One. 2014;9(10):e109634.CrossRef Yang H, Song Z, Yang G-P, Zhang B-K, Chen M, Wu T, Guo R. The ALDH2 rs671 polymorphism affects post-stroke epilepsy susceptibility and plasma 4-HNE levels. PLoS One. 2014;9(10):e109634.CrossRef
24.
go back to reference Luo X-J, Liu B, Ma Q-L, Peng J. Mitochondrial aldehyde dehydrogenase, a potential drug target for protection of heart and brain from ischemia/reperfusion injury. Curr Drug Targets. 2014;15(10):948–55.PubMed Luo X-J, Liu B, Ma Q-L, Peng J. Mitochondrial aldehyde dehydrogenase, a potential drug target for protection of heart and brain from ischemia/reperfusion injury. Curr Drug Targets. 2014;15(10):948–55.PubMed
25.
go back to reference Chen L, Zhou J-P, Kuang D-B, Tang J, Li Y-J, Chen X-P. 4-HNE increases intracellular ADMA levels in cultured HUVECs: evidence for miR-21-dependent mechanisms. PLoS One. 2013;8(5):e64148.CrossRef Chen L, Zhou J-P, Kuang D-B, Tang J, Li Y-J, Chen X-P. 4-HNE increases intracellular ADMA levels in cultured HUVECs: evidence for miR-21-dependent mechanisms. PLoS One. 2013;8(5):e64148.CrossRef
26.
go back to reference Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino J, Siegel N, Leimgruber R, Feder J. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989;84(5):1470–8.CrossRef Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino J, Siegel N, Leimgruber R, Feder J. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989;84(5):1470–8.CrossRef
27.
go back to reference Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18(14):3964–72.CrossRef Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18(14):3964–72.CrossRef
28.
go back to reference Virmani R, Kolodgie FD, Yahagi K. Epidemiology and pathophysiology of coronary artery disease. In: Practical Interventional Cardiology. US: CRC Press; 2017. p. 3–15. Virmani R, Kolodgie FD, Yahagi K. Epidemiology and pathophysiology of coronary artery disease. In: Practical Interventional Cardiology. US: CRC Press; 2017. p. 3–15.
Metadata
Title
Relationship between ALDH2 genotype and in-stent restenosis in Chinese Han patients after percutaneous coronary intervention
Authors
Lizhi Lv
Weijie Ye
Peiyuan Song
Yubin Chen
Jing Yang
Congmin Zhang
Xiaoping Chen
Fanyan Luo
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Clopidogrel
Published in
BMC Cardiovascular Disorders / Issue 1/2019
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-019-1161-9

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