{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:21Z","timestamp":1760146941022,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["\u0410\u042023490249","\u0410\u042019677442","AP14869903","BR24993023","BR24992841","BR21881970","211123CRP1608","021220CRP2222"],"award-info":[{"award-number":["\u0410\u042023490249","\u0410\u042019677442","AP14869903","BR24993023","BR24992841","BR21881970","211123CRP1608","021220CRP2222"]}]},{"name":"Nazarbayev University CRP projects","award":["\u0410\u042023490249","\u0410\u042019677442","AP14869903","BR24993023","BR24992841","BR21881970","211123CRP1608","021220CRP2222"],"award-info":[{"award-number":["\u0410\u042023490249","\u0410\u042019677442","AP14869903","BR24993023","BR24992841","BR21881970","211123CRP1608","021220CRP2222"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Despite the high progress that has been made in the field of cardiology, the left ventricular assist device (LVAD) can still cause complications (thrombosis\/bleeding) in heart failure (HF) patients after implantation. Complications develop due to the incorrect dose of antithrombotic therapy, due to the influence of the non-physiological shear stress of the device, and also due to inherited genetic polymorphisms. Therefore, the aim of our study is to identify the influence of the genetic polymorphisms on complication development in HF patients with implanted LVADs with prescribed antiplatelet therapy. Methods: Our study investigated 98 HF patients with\/without complications who were genotyped for 21 single-nucleotide polymorphisms (SNPs) associated with cardiovascular events, the coagulation system, and the metabolism of warfarin and aspirin drugs. This study performed a more detailed analysis on genetic polymorphism in the UGT1A6 gene and its influence on aspirin dose. Results: SNP rs2070959 in the UGT1A6 gene showed a significant association with the group of HF patients with complications [(OR (95% CI): 4.40 (1.06\u201318.20), p = 0.044]. The genetic polymorphism of rs2070959 in the UGT1A6 gene showed a significant association in HF patients who received aspirin treatment on the 12th month after LVAD implantation [OR (95% CI): 5.10 (1.31\u201319.87), p = 0.018]. Moreover, our genotype distribution analysis showed that the GG genotype of rs2070959 in the UGT1A6 gene was significantly higher in the group with aspirin treatment than without treatment after the 12th month of treatment (50.0% vs. 0%, p = 0.008), especially in the group of patients with complications. A higher frequency of the GG genotype with long-lasting aspirin therapy up to the 12th month showed that 100 mg of aspirin was not an effective dose in the group of patients with complications. Conclusions: Our study identified that genotyping for genetic polymorphism rs2070959 in the UGT1A6 gene could predict the recommended dose of aspirin in HF patients, which could help to prevent and predict complication development after LVAD implantation.<\/jats:p>","DOI":"10.3390\/jcm14010035","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T19:27:46Z","timestamp":1735154866000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Genetic Polymorphism on Complication Development in Heart Failure Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Madina R.","family":"Zhalbinova","sequence":"first","affiliation":[{"name":"National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8245-2400","authenticated-orcid":false,"given":"Saule E.","family":"Rakhimova","sequence":"additional","affiliation":[{"name":"National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Eurasian Society of Personalize Medicine, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulan A.","family":"Kozhamkulov","sequence":"additional","affiliation":[{"name":"National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Eurasian Society of Personalize Medicine, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-2424","authenticated-orcid":false,"given":"Kenes R.","family":"Akilzhanov","sequence":"additional","affiliation":[{"name":"Department of Medicine, Semey Medical University, Pavlodar Branch, Pavlodar 140000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurlan K.","family":"Shaimardanov","sequence":"additional","affiliation":[{"name":"Department of Medicine, Semey Medical University, Semey 071400, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulbanu A.","family":"Akilzhanova","sequence":"additional","affiliation":[{"name":"Department of Medicine, Semey Medical University, Pavlodar Branch, Pavlodar 140000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2000-4821","authenticated-orcid":false,"given":"Joseph H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Sergievsky Center, Taub Institute, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuriy V.","family":"Pya","sequence":"additional","affiliation":[{"name":"National Research Cardiac Surgery Center, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makhabbat S.","family":"Bekbossynova","sequence":"additional","affiliation":[{"name":"National Research Cardiac Surgery Center, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-8355","authenticated-orcid":false,"given":"Ainur R.","family":"Akilzhanova","sequence":"additional","affiliation":[{"name":"National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Eurasian Society of Personalize Medicine, Astana 010000, Kazakhstan"},{"name":"Department of General Biology and Genomics, L. N. Gumilyov Eurasian National University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Berardi, C., Bravo, C.A., Li, S., Khorsandi, M., Keenan, J.E., Auld, J., Rockom, S., Beckman, J.A., and Mahr, C. (2022). The history of durable left ventricular assist devices and comparison of outcomes: HeartWare, HeartMate II, HeartMate 3, and the future of mechanical circulatory support. J. Clin. Med., 11.","DOI":"10.3390\/jcm11072022"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1097\/MAT.0000000000000390","article-title":"Effect of CYP2C9 and VKORC1 gene variants on warfarin response in patients with continuous-flow left ventricular assist devices","volume":"62","author":"Topkara","year":"2016","journal-title":"ASAIO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1002\/ejhf.2275","article-title":"Aspirin and left ventricular assist devices: Rationale and design for the international randomized, placebo-controlled, non-inferiority ARIES HM3 trial","volume":"23","author":"Mehra","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.healun.2013.11.001","article-title":"Interagency registry for mechanically assisted circulatory support (INTERMACS) analysis of pump thrombosis in the heartmate II left ventricular assist device","volume":"33","author":"Kirklin","year":"2014","journal-title":"J. Heart Lung Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/HCO.0000000000000284","article-title":"Bleeding and thrombosis in chronic ventricular assist device therapy: Focus on platelets","volume":"31","author":"Koliopoulou","year":"2016","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1097\/MAT.0000000000000722","article-title":"Quantitative characterization of shear-induced platelet receptor shedding: Glycoprotein Ibalpha, glycoprotein VI, and glycoprotein IIb\/IIIa","volume":"64","author":"Chen","year":"2018","journal-title":"ASAIO J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhalbinova, M.R., Rakhimova, S.E., Kozhamkulov, U.A., Akilzhanova, G.A., Chinybayeva, A.A., Akilzhanov, K.R., Shaimardanov, N.K., Kuanysheva, A.G., Lee, J.H., and Kairov, U.Y. (2023). Role of genetic polymorphisms in the development of complications in patients with implanted left ventricular assist devices: HeartWare, HeartMate II, and HeartMate 3. J. Clin. Med., 12.","DOI":"10.3390\/jcm12237235"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1097\/MAT.0000000000001064","article-title":"Influence of different antithrombotic regimens on platelet-mediated thrombin generation in patients with left ventricular assist devices","volume":"66","author":"Consolo","year":"2020","journal-title":"ASAIO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.healun.2018.03.002","article-title":"Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study","volume":"37","author":"Netuka","year":"2018","journal-title":"J. Heart Lung Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1001\/jama.2023.23204","article-title":"Aspirin and hemocompatibility events with a left ventricular assist device in advanced heart failure: The ARIES-HM3 Randomized Clinical Trial","volume":"330","author":"Mehra","year":"2023","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/aor.13445","article-title":"Device-induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding","volume":"43","author":"Chen","year":"2019","journal-title":"Artif. Organs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/MAT.0000000000000231","article-title":"Prevalence of Warfarin Genotype Polymorphisms in Patients with Mechanical Circulatory Support","volume":"61","author":"Awad","year":"2015","journal-title":"ASAIO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1016\/j.healun.2024.02.091","article-title":"The Impact of Genetic Polymorphism on Complications Development in Heart Failure Patients","volume":"43","author":"Zhalbinova","year":"2024","journal-title":"J. Heart Lung Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhalbinova, M.R., Rakhimova, S.E., Kozhamkulov, U.A., Akilzhanova, G.A., Kaussova, G.K., Akilzhanov, K.R., Pya, Y.V., Lee, J.H., Bekbossynova, M.S., and Akilzhanova, A.R. (2022). Association of genetic polymorphisms with complications of implanted LVAD devices in patients with congestive heart failure: A kazakhstani study. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050744"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"998","DOI":"10.2174\/138920009790711814","article-title":"Pharmacogenomics in Aspirin Intolerance","volume":"10","author":"Martinez","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/01.fpc.0000236339.79916.07","article-title":"UGT1A6 polymorphism and salicylic acid glucuronidation following aspirin","volume":"17","author":"Chen","year":"2007","journal-title":"Pharmacogenet. Genom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/clpt.2011.185","article-title":"Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing","volume":"90","author":"Johnson","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/cpt.1755","article-title":"Genetic factors influencing warfarin dose in black-african patients: A systematic review and meta-analysis","volume":"107","author":"Asiimwe","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1365-2125.2005.02495.x","article-title":"Polymorphisms in genes encoding acetylsalicylic acid metabolizing enzymes are unrelated to upper gastrointestinal health in cardiovascular patients on acetylsalicylic acid","volume":"60","author":"Huybers","year":"2005","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2174\/1389200053586064","article-title":"Polymorphism of UDP-Glucuronosyltransferase and drug metabolism","volume":"6","author":"Maruo","year":"2005","journal-title":"Curr. Drug Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10555-017-9675-z","article-title":"Beyond COX-1: The effects of aspirin on platelet biology and potential mechanisms of chemoprevention","volume":"36","author":"Ornelas","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.healun.2020.03.001","article-title":"Effect of aspirin dose on hemocompatibility-related outcomes with a magnetically levitated left ventricular assist device: An analysis from the MOMENTUM 3 study","volume":"39","author":"Saeed","year":"2020","journal-title":"J. Heart Lung Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.healun.2015.06.018","article-title":"Safety of reduced anti-thrombotic strategies in HeartMate II patients: A one-year analysis of the US-TRACE Study","volume":"34","author":"Katz","year":"2015","journal-title":"J. Heart Lung Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e002296","DOI":"10.1161\/CIRCHEARTFAILURE.115.002296","article-title":"Antiplatelet Therapy and Adverse Hematologic Events During Heart Mate II Support","volume":"9","author":"Saeed","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.athoracsur.2016.07.072","article-title":"Outcomes in HeartMate II patients with no antiplatelet therapy: 2-year results from the European TRACE Study","volume":"103","author":"Netuka","year":"2017","journal-title":"Ann. Thorac. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.healun.2013.12.001","article-title":"An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial","volume":"33","author":"Najjar","year":"2014","journal-title":"J. Heart Lung Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.healun.2013.04.004","article-title":"HeartWare ventricular assist system for bridge to transplant: Combined results of the bridge to transplant and continued access protocol trial","volume":"32","author":"Slaughter","year":"2013","journal-title":"J. Heart Lung Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sheth, H., Northwood, E., Ulrich, C.M., Scherer, D., Elliott, F., Barrett, J.H., Forman, D., Wolf, C.R., Smith, G., and Jackson, M.S. (2018). Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192223"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/gcc.22167","article-title":"Genetic variation in UGT genes modify the associations of NSAIDs with risk of colorectal cancer: Colon cancer family registry","volume":"53","author":"Scherer","year":"2014","journal-title":"Genes Chromosomes Cancer"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/1\/35\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:00:03Z","timestamp":1760115603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/1\/35"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,25]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["jcm14010035"],"URL":"https:\/\/doi.org\/10.3390\/jcm14010035","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,12,25]]}}}