The Impact of Genetic Polymorphism on Complication Development in Heart Failure Patients

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> SNP rs2070959 in the <i>UGT1A6</i> gene showed a significant association with the group of HF patients with complications [(OR (95% CI): 4.40 (1.06-18.20), <i>p</i> = 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), <i>p</i> = 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%, <i>p</i> = 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. <b>Conclusions:</b> 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.

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Publication Details

Journal
Journal of Clinical Medicine
Published
2024-12-25
DOI
https://doi.org/10.3390/jcm14010035
Primary Topic
Mechanical Circulatory Support Devices
Type
article
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article

The Impact of Genetic Polymorphism on Complication Development in Heart Failure Patients

Ainur R. Akilzhanova, M. Zhalbinova, Joseph Hyungwoo Lee, Gulbanu Akilzhanova et al.
Journal of Clinical Medicine
Mechanical Circulatory Support Devices
article

The Impact of Genetic Polymorphism on Complication Development in Heart Failure Patients

Ainur R. Akilzhanova, M. Zhalbinova, Joseph Hyungwoo Lee, Gulbanu Akilzhanova, Kenes R. Akilzhanov, Nurlan K. Shaimardanov, Saule Rakhimova, Yuriy V. Pya, Ulan Kozhamkulov, Makhabbat S. Bekbossynova
article en

Abstract

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> SNP rs2070959 in the <i>UGT1A6</i> gene showed a significant association with the group of HF patients with complications [(OR (95% CI): 4.40 (1.06-18.20), <i>p</i> = 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), <i>p</i> = 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%, <i>p</i> = 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. <b>Conclusions:</b> 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.

Journal of Clinical MedicineVol. 14(1)
L. N. Gumilyov Eurasian National University (KZ), Columbia University Irving Medical Center (US), Semey Medical University (KZ), Nazarbayev University (KZ)
Good health and well-being
Openalex Percentile: Top 77%
Mechanical Circulatory Support Devices
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