Genetic Factors of Renin-Angiotensin System Associated with Major Bleeding for Patients Treated with Direct Oral Anticoagulants

• Main Authors: Jeong Yee (Author), Tae-Jin Song (Author), Ha-Young Yoon (Author), Junbeom Park (Author), Hye-Sun Gwak (Author)
• Format: Book
• Published: MDPI AG, 2022-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics14020231; 1999-4923
• Keywords: direct oral anticoagulants; bleeding; renin-angiotensin system; polymorphisms; pharmacogenomics; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 2, p 231 (2022)

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.