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

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Feb 26

PMID 35213964

Authors

Jeong Yee

Tae-Jin Song

Ha-Young Yoon

Junbeom Park

Hye-Sun Gwak

Affiliations

Soon will be listed here.

Abstract

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, , , , , and ). 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.

Citing Articles

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Zubiaur P, Abad-Santos F Pharmaceutics. 2023; 15(1).

PMID: 36678742 PMC: 9867244. DOI: 10.3390/pharmaceutics15010113.

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