An Exploratory Association Analysis of <i>ABCB</i>₁ rs1045642 and <i>ABCB</i>₁ rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban

• Main Authors: Adela-Nicoleta Roşian, Mihaela Iancu, Adrian Pavel Trifa, Ştefan Horia Roşian, Cristina Mada, Cornelia Paula Gocan, Teodora Niţă, Sabina Istratoaie, Paul-Mihai Boarescu, Anca Dana Buzoianu
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Journal of Personalized Medicine
• Subjects: <i>ABCB</i>₁; apixaban; bleedings; clinical practice; dabigatran; pharmacogenomics
• Online Access: https://www.mdpi.com/2075-4426/10/3/133

(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, <i>ABCB</i>₁ gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: <i>ABCB</i>₁ rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two <i>ABCB</i>₁ SNPs and the risk of bleeding (<i>p</i> > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (<i>p</i> > 0.05) except for the TG haplotype which had a trend toward statistical significance (<i>p</i> = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied <i>ABCB</i>₁ variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.