Zhalbinova Madina R, Rakhimova Saule E, Kozhamkulov Ulan A, Akilzhanov Kenes R, Shaimardanov Nurlan K, Akilzhanova Gulbanu A, Lee Joseph H, Pya Yuriy V, Bekbossynova Makhabbat S, Akilzhanova Ainur R
National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan.
Eurasian Society of Personalize Medicine, Astana 010000, Kazakhstan.
J Clin Med. 2024 Dec 25;14(1):35. doi: 10.3390/jcm14010035.
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. 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. SNP rs2070959 in the gene showed a significant association with the group of HF patients with complications [(OR (95% CI): 4.40 (1.06-18.20), = 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 (1.31-19.87), = 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%, = 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. 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.
尽管心脏病学领域已取得了很大进展，但左心室辅助装置（LVAD）在植入后仍可能导致心力衰竭（HF）患者出现并发症（血栓形成/出血）。并发症的发生是由于抗血栓治疗剂量不正确、装置非生理性剪切应力的影响以及遗传多态性。因此，我们研究的目的是确定遗传多态性对接受规定抗血小板治疗的植入LVAD的HF患者并发症发生的影响。我们的研究调查了98例有/无并发症的HF患者，对其进行了与心血管事件、凝血系统以及华法林和阿司匹林药物代谢相关的21个单核苷酸多态性（SNP）的基因分型。本研究对UGT1A6基因的遗传多态性及其对阿司匹林剂量的影响进行了更详细的分析。该基因中的SNP rs2070959与有并发症的HF患者组显著相关[比值比（95%置信区间）：4.40（1.06 - 18.20），P = 0.044]。UGT1A6基因中rs2070959的遗传多态性在LVAD植入后第12个月接受阿司匹林治疗的HF患者中显著相关[比值比（95%置信区间）：5.10（1.31 - 19.87），P = 0.018]。此外，我们的基因型分布分析表明，治疗12个月后，接受阿司匹林治疗组中UGT1A6基因rs2070959的GG基因型显著高于未治疗组（50.0%对0%，P = 0.008），尤其是在有并发症的患者组中。在持续使用阿司匹林治疗至第12个月的患者中，GG基因型频率较高表明，100 mg阿司匹林对有并发症的患者组不是有效剂量。我们的研究发现，对UGT1A6基因中遗传多态性rs2070959进行基因分型可以预测HF患者的阿司匹林推荐剂量，这有助于预防和预测LVAD植入后的并发症发生。
