BACKGROUND: We sought to identify gene polymorphisms that confer susceptibility to in-stent restenosis after coronary artery bare-metal stenting in a Central European population. METHODS: 160 controls without post-percutaneous coronary intervention in-stent restenosis were matched for age, sex, vessel diameter, and diabetes to 160 consecutive cases involving in-stent restenosis of the target lesion within 12 months. Using real time polymerase chain reaction and melting-curve analysis, we detected 13 single-nucleotide polymorphisms in 11 candidate genes - rs1803274 (BCHE gene), rs529038 (ROS1), rs1050450 (GPX1), rs1800849 (UCP3), rs17216473 (ALOX5AP), rs7412, rs429358 (ApoE), rs2228570 (VDR), rs7041, rs4588 (GC), rs1799986 (LRP1) and rs2228671 (LDLR). Multivariable logistic regression was used to test for associations. RESULTS: The rs1803274 polymorphism of BCHE was significantly associated with in-stent restenosis (OR 1.934; 95 % CI: 1.181-3.166; p = 0.009). No association was found with the other studied SNPs. CONCLUSIONS: The A allele of rs1803274 represents a risk factor for in-stent restenosis in Central European patients after percutaneous coronary intervention with bare-metal stent implantation.

Blood Center University Hospital of Ostrava Ostrava Czech Republic

Department of Biomedical Sciencies Medical Faculty University of Ostrava Ostrava Czech Republic

Department of Cardiovascular Diseases University Hospital Ostrava Ostrava Czech Republic

Department of Clinical Studies Medical Faculty University of Ostrava Syllabova 19 Ostrava Zabreh 703 00 Czech Republic

Department of Laboratory Medicine University Hospital Ostrava Ostrava Czech Republic

Department of Medical Biophysics Palacky University Olomouc Czech Republic

Department of Medical Genetics University Hospital Ostrava Ostrava Czech Republic

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Kim MS, Dean LS. In-Stent Restenosis. Cardiovasc Ther. 2011;29:190–198. doi: 10.1111/j.1755-5922.2010.00155.x. PubMed DOI

Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB, III, Loop FD, et al. Guidelines for percutaneous transluminal coronary angioplasty: A report of the American College of Cardiology/American Heart Association Task Force on the Assesment of Diagnostic and Therapeutic Cardiovascular Procedures. Circulation. 1988;78(2):486–502. doi: 10.1161/01.CIR.78.2.486. PubMed DOI

Oguri M, Kato K, Hibino T, Yokoi K, Segawa T, Matsuo H, et al. Genetic risk for restenosis after coronary stenting. Atherosclerosis. 2007;194:e172–e178. doi: 10.1016/j.atherosclerosis.2006.12.019. PubMed DOI

Oguri M, Kato K, Hibino T, Yokoi K, Segawa T, Matsuo H, et al. Identification of a polymorphism of UCP3 associated with recurrent in-stent restenosis of coronary arteries. Int J Mol Med. 2007;20:533–538. PubMed

Shah SH, Hauser ER, Crosslin D, Wang L, Haynes C, Connelly J. ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention. Atherosclerosis. 2008;201:148–154. doi: 10.1016/j.atherosclerosis.2008.01.011. PubMed DOI PMC

Xu H, Li H, Liu J, Zhu D, Wang Z, Chen A. Meta-Analysis of Apolipoprotein E Gene Polymorphism and Susceptibility of Myocardial Infarction. PLoS One. 2014;9(8):e104608. doi: 10.1371/journal.pone.0104608. PubMed DOI PMC

Bennet AM, Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A. Association of Apolipoprotein E Genotypes With Lipid Levels and Coronary Risk. JAMA. 2007;298(11):1300–1311. doi: 10.1001/jama.298.11.1300. PubMed DOI

Chen S, Law CS, Gardner DG. Vitamin D-dependent suppression of endothelin-induced vascular smooth muscle cell proliferation through inhibition of CDK2 activity. J Steroid Biochem Mol Biol. 2010;118:135–141. doi: 10.1016/j.jsbmb.2009.11.002. PubMed DOI PMC

Holick MF. Vitamin D, deficiency. N Engl J Med. 2007;357:266–281. doi: 10.1056/NEJMra070553. PubMed DOI

Gupta GK, Agrawal T, Del Core MG, Hunter WJ, Agrawal DK. Decreased Expression of Vitamin D Receptors in Neointimal Lesions following Coronary Artery Angioplasty in Atherosclerotic Swine. PLoS One. 2012;7(8):e42789. doi: 10.1371/journal.pone.0042789. PubMed DOI PMC

Bujo H, Saito Y. Lipoprotein Receptor Family Modulation of Smooth Muscle Cell Migration by Members of the Low-Density Lipoprotein Receptor Family. Arterioscler Thromb Vasc Biol. 2006;26:1246–1252. doi: 10.1161/01.ATV.0000219692.78477.17. PubMed DOI

Dunnen JT, Antonarakis SE. Mutation Nomenclature Extensions and Suggestions to Describe Complex Mutations: A Discussion. Hum Mutat. 2000;15:7–12. doi: 10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N. PubMed DOI

Byrne RA, Joner M, Massberg S, Kastrati A. Restenosis in bare metal and drug-eluting stents. In: Escaned J, Serruys PW, editors. Coronary stenosis, imaging, structure and physiology. 1. Toulouse, France: Europa Edition; 2010. pp. 475–496.

Valle A, O’Connor DT, Taylor PW, Zhu G, Montgomery GW, Slagboom PE, et al. Pseudocholinesterase: association with the metabolic syndrome and identification of 2 gene loci affecting activity. Clin Chem. 2006;52:1014–1020. doi: 10.1373/clinchem.2005.065052. PubMed DOI

Zhou G, Marathe GK, Hartiala J, Hazen SL, Allayee H, Tang WWH. Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2) J Biol Chem. 2013;288(17):11940–11948. doi: 10.1074/jbc.M112.427674. PubMed DOI PMC

Nassar BA, Rockwood K, Kirkland SA, Ransom TP, Darvesh S. Improved prediction of early-onset coronary artery disease using APOE epsilon 4, BChE-K, PPAR gamma2 Pro12 and ENOS T-786C in a polygenic model. Clin Biochem. 2006;39:109–114. doi: 10.1016/j.clinbiochem.2005.10.002. PubMed DOI

Scacchi R, Ruggeri M, Corbo MR. Variation of the butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) genes in coronary artery disease. Clin Chim Acta. 2011;412:1341–1344. doi: 10.1016/j.cca.2011.03.033. PubMed DOI

Shuvalova YA, Kaminnyi AI, Meshkov AN, Shirokov RO, Samko AN. Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis. Mol Cell Biochem. 2012;370:241–249. doi: 10.1007/s11010-012-1419-3. PubMed DOI

Verschuren JJ, Trompet S, Postmus I, Sampietro ML, Heijmans BT. Systematic Testing of Literature Reported Genetic Variation Associated with Coronary Restenosis: Results of the GENDER Study. PLoS One. 2012;7(8):e42401. doi: 10.1371/journal.pone.0042401. PubMed DOI PMC

Girelli D, Martinelli N, Trabetti E, Olivieri O, Cavallari U, Malerba G, et al. ALOX5AP gene variants and risk of coronary artery disease: an angiography-based study. Eur J Hum Genet. 2007;15:959–966. doi: 10.1038/sj.ejhg.5201854. PubMed DOI

Koch W, Mehilli J, Pfeufer A, Schömig A, Kastrati A. Apolipoprotein E gene polymorphisms and thrombosis and restenosis after coronary artery stenting. J Lipid Res. 2004;45:2221–2226. doi: 10.1194/jlr.M400148-JLR200. PubMed DOI

Ali ZA, Alp NJ, Lupton H, Arnold N, Bannister T, Hu Y, et al. Increased In-Stent Stenosis in ApoE Knockout Mice. Insights from a Novel Mouse Model of Balloon Angioplasty and Stenting. Arterioscler Thromb Vasc Biol. 2007;27:833–840. doi: 10.1161/01.ATV.0000257135.39571.5b. PubMed DOI

Monraats PS, Fang Y, Pons D, Pires NMM, Pols HAP, Zwinderman AH. Vitamin D receptor: A new risk marker for clinical restenosis after percutaneous coronary intervention. Expert Opin Ther Tar. 2010;14(3):243–251. doi: 10.1517/14728220903520929. PubMed DOI

Sun Z, Marzouq A, Almutairi D. Diagnostic accuracy of 64 multislice CT angiography in the assessment of coronary in-stent restenosis: A meta-analysis. Eur J Radiol. 2010;73:266–273. doi: 10.1016/j.ejrad.2008.10.025. PubMed DOI

Kumbhani DJ, Ingelmo CP, Schoenhagen P, Curtin RJ, Flamm SD, Desai MY. Meta-analysis of diagnostic efficacy of 64-slice Computed Tomography in the evaluation of coronary in-stent restenosis. Am J Cardiol. 2009;103:1675–1681. doi: 10.1016/j.amjcard.2009.02.024. PubMed DOI