ABCB1 gene single nucleotide variants and haplotypes in atrial fibrillation patients experiencing adverse events on direct oral anticoagulation: a whole gene exome sequencing study.

Single-nucleotide variants (SNVs) of ABCB1 gene encoding glycoprotein P might be connected with increased or decreased levels of direct oral anticoagulants (DOAC), and therefore with DOAC-related adverse bleeding or embolism. The aim of this study was to perform a targeted exome sequencing (TES) of ABCB1 gene in DOAC-treated patients with atrial fibrillation, who experienced a DOAC-related adverse event (AE) during the therapy. Targeted next generation sequencing was employed to examine SNVs in ABCB1 gene, which served as the basis for haplotype analysis. The study enrolled 33 patients with an AE (13 patients with bleeding and 20 patients with embolic stroke) and 33 patients tolerating long-term DOAC therapy without any AE (controls). The PLINK software was used to compare the differences between the groups. Fisher's test was employed for a standard case/control allelic association, and the chi-squared test was applied to test haplotype associations in contingency tables. In patients with DOAC-related bleeding compared with controls, no significant differences were found in all the examined SNVs; however, there were significant differences in the presence of AAAGAGCT (11.5%vs.1.6%,p<0.05) and AGAG (11.1vs.1.7%,p<0.05) haplotypes. Compared to controls, patients with stroke had a minor allele observed more frequently in rs2235033 (62.5%vs.39.4%,p<0.05), and significant differences were also found in the presence of AAAGAACT (19.3vs.39.0%,p<0.05), GGCGGGAT (19.5vs.6.4%,p<0.05), AGAA (30.8vs.51.4%,p<0.05), CGGG (23.1vs.7.6%,p<0.05) haplotypes. This study found significant differences in the selected rs2235033 SNV and in several ABCB1 gene common haplotypes in patients with DOAC-related AE.