Related Experiment Video
Updated: Jun 3, 2025
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
The Impact of Genetic Polymorphism on Complication Development in Heart Failure Patients
Madina R Zhalbinova1, Saule E Rakhimova1,2, Ulan A Kozhamkulov1,2
1National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan.
Insights
Genetic variations like UGT1A6 rs2070959 influence aspirin effectiveness in heart failure patients with left ventricular assist devices (LVADs). Genotyping can help personalize antiplatelet therapy to prevent complications such such as thrombosis and bleeding.
Area of Science:
- Cardiology
- Pharmacogenomics
- Medical Devices
Background:
- Left ventricular assist devices (LVADs) improve heart failure (HF) management but can lead to thrombosis or bleeding complications.
- These complications are often linked to suboptimal antithrombotic therapy dosing and non-physiological shear stress from the device.
- Genetic factors, including inherited polymorphisms, also play a role in patient outcomes after LVAD implantation.
Purpose of the Study:
- To investigate the influence of genetic polymorphisms on the development of complications in HF patients receiving antiplatelet therapy post-LVAD implantation.
- To specifically analyze the impact of UGT1A6 gene polymorphisms on aspirin dosage and efficacy.
Main Methods:
- Genotyping of 98 HF patients (with/without complications) for 21 single-nucleotide polymorphisms (SNPs) related to cardiovascular events, coagulation, and drug metabolism.
- Detailed analysis of UGT1A6 gene polymorphisms, particularly rs2070959, and their association with aspirin treatment and complications.
Main Results:
- SNP rs2070959 in the UGT1A6 gene was significantly associated with complications in HF patients post-LVAD (OR 4.40, p=0.044).
- This polymorphism also showed a significant association with aspirin treatment at 12 months post-implantation (OR 5.10, p=0.018).
- The GG genotype of rs2070959 was more frequent in patients with complications on long-term aspirin therapy, indicating 100 mg aspirin was ineffective in this group.
Conclusions:
- Genotyping for UGT1A6 rs2070959 can predict aspirin dosage requirements in HF patients with LVADs.
- Personalized antiplatelet therapy based on genetic profiles may help prevent and predict complications after LVAD implantation.
Abstract:
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 (1.06-18.20), 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 (1.31-19.87), 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.
More Related Videos
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
14:35Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Related Concept Videos
01:17Pathophysiology of Heart Failure
01:26Imbalances in Cardiac Output
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:22Heart Failure Drugs: Diuretics
01:25Genetic Variation
Genes exist in different versions called alleles,...
01:28Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...