Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants
The purpose of this study was to identify the renin–angiotensin system (RAS)-related genetic factors associated with bleeding and develop the bleeding risk scoring system in patients receiving direct oral anticoagulants (DOACs). This study was a retrospective analysis of prospectively collected samp...
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MDPI AG
2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/231 |
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| author | Jeong Yee Tae-Jin Song Ha-Young Yoon Junbeom Park Hye-Sun Gwak |
| author_facet | Jeong Yee Tae-Jin Song Ha-Young Yoon Junbeom Park Hye-Sun Gwak |
| author_sort | Jeong Yee |
| collection | DOAJ |
| description | The purpose of this study was to identify the renin–angiotensin system (RAS)-related genetic factors associated with bleeding and develop the bleeding risk scoring system in patients receiving direct oral anticoagulants (DOACs). This study was a retrospective analysis of prospectively collected samples from June 2018 to May 2020. To investigate the associations between RAS-related genetic factors and major bleeding, we selected 16 single nucleotide polymorphisms (SNPs) from five genes (namely, <i>AGT</i>, <i>REN</i>, <i>ACE</i>, <i>AGTR1</i>, and <i>AGTR2</i>). Multivariable logistic regression analysis was employed to investigate the independent risk factors for bleeding and to develop a risk scoring system. A total of 172 patients were included in the analysis, including 33 major bleeding cases. Both old age (≥65 years) and moderate to severe renal impairment (CrCl < 50 mL/min) increased the risk of bleeding in the multivariable analysis. Among RAS-related polymorphisms, patients carrying TT genotype of rs5050 and A allele of rs4353 experienced a 3.6-fold (95% CI: 1.4–9.3) and 3.1-fold (95% CI: 1.1–9.3) increase in bleeding, respectively. The bleeding risk increased exponentially with a higher score; the risks were 0%, 2.8%, 16.9%, 32.7%, and 75% in patients with 0, 1, 2, 3, and 4 points, respectively. Although this study is limited to a retrospective study design, this is the first study to suggest RAS-related genetic markers and risk scoring systems, including both clinical and genetic factors, for major bleeding in patients receiving DOAC treatment. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:15:20Z |
| publishDate | 2022-01-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-cf7f971bcf4c4178bb9c6dabf4633fce2023-11-23T21:35:50ZengMDPI AGPharmaceutics1999-49232022-01-0114223110.3390/pharmaceutics14020231Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral AnticoagulantsJeong Yee0Tae-Jin Song1Ha-Young Yoon2Junbeom Park3Hye-Sun Gwak4College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaDepartment of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul 07804, KoreaCollege of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaDivision of Cardiology, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul 07985, KoreaCollege of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaThe purpose of this study was to identify the renin–angiotensin system (RAS)-related genetic factors associated with bleeding and develop the bleeding risk scoring system in patients receiving direct oral anticoagulants (DOACs). This study was a retrospective analysis of prospectively collected samples from June 2018 to May 2020. To investigate the associations between RAS-related genetic factors and major bleeding, we selected 16 single nucleotide polymorphisms (SNPs) from five genes (namely, <i>AGT</i>, <i>REN</i>, <i>ACE</i>, <i>AGTR1</i>, and <i>AGTR2</i>). Multivariable logistic regression analysis was employed to investigate the independent risk factors for bleeding and to develop a risk scoring system. A total of 172 patients were included in the analysis, including 33 major bleeding cases. Both old age (≥65 years) and moderate to severe renal impairment (CrCl < 50 mL/min) increased the risk of bleeding in the multivariable analysis. Among RAS-related polymorphisms, patients carrying TT genotype of rs5050 and A allele of rs4353 experienced a 3.6-fold (95% CI: 1.4–9.3) and 3.1-fold (95% CI: 1.1–9.3) increase in bleeding, respectively. The bleeding risk increased exponentially with a higher score; the risks were 0%, 2.8%, 16.9%, 32.7%, and 75% in patients with 0, 1, 2, 3, and 4 points, respectively. Although this study is limited to a retrospective study design, this is the first study to suggest RAS-related genetic markers and risk scoring systems, including both clinical and genetic factors, for major bleeding in patients receiving DOAC treatment.https://www.mdpi.com/1999-4923/14/2/231direct oral anticoagulantsbleedingrenin–angiotensin systempolymorphismspharmacogenomics |
| spellingShingle | Jeong Yee Tae-Jin Song Ha-Young Yoon Junbeom Park Hye-Sun Gwak Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants Pharmaceutics direct oral anticoagulants bleeding renin–angiotensin system polymorphisms pharmacogenomics |
| title | Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants |
| title_full | Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants |
| title_fullStr | Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants |
| title_full_unstemmed | Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants |
| title_short | Genetic Factors of Renin–Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants |
| title_sort | genetic factors of renin angiotensin system associated with major bleeding for patients treated with direct oral anticoagulants |
| topic | direct oral anticoagulants bleeding renin–angiotensin system polymorphisms pharmacogenomics |
| url | https://www.mdpi.com/1999-4923/14/2/231 |
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