Roşian Adela-Nicoleta, Iancu Mihaela, Trifa Adrian Pavel, Roşian Ştefan Horia, Mada Cristina, Gocan Cornelia Paula, Niţă Teodora, Istratoaie Sabina, Boarescu Paul-Mihai, Buzoianu Anca Dana
Department of Pharmacology, Toxicology and Clinical Pharmacology, "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania.
"Niculae Stăncioiu" Heart Institute Cluj-Napoca, 19-21 Calea Moților Street, 400001 Cluj-Napoca, Romania.
J Pers Med. 2020 Sep 18;10(3):133. doi: 10.3390/jpm10030133.
(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, gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: 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 SNPs and the risk of bleeding ( > 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 ( > 0.05) except for the TG haplotype which had a trend toward statistical significance ( = 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 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.
(1) 背景：非维生素K口服抗凝剂（NOACs）治疗患者出血并发症的处理是临床实践中的一个重要问题。达比加群和阿哌沙班均为P-糖蛋白的底物，因此，基因变异可能有助于个体化NOACs治疗，尤其是在高危患者中。(2) 方法：在218例接受达比加群或阿哌沙班治疗的房颤患者中测定rs1045642和rs4148738（年龄70.94±9.04岁；男性占51.83%）。(3) 结果：7.34%接受NOACs治疗的患者出现非大出血。基于四种遗传模型的逻辑检验模型显示，两个单核苷酸多态性（SNP）的变异基因型与出血风险之间无显著关联（P>0.05）。在四种双位点单倍型中，TA和CA单倍型在接受NOACs治疗且发生出血的患者中频率最高，可能与出血并发症易感性呈正相关（OR分别为1.04和1.91）。逻辑模型发现，除TG单倍型有统计学意义趋势（P=0.092）外，估计单倍型与出血无显著关联（P>0.05）。在出血危险因素中，仅年龄>70岁和卒中/短暂性脑缺血发作有统计学意义趋势。(4) 结论：我们发现，在接受NOACs治疗的患者中，所研究的变异基因型与非大出血风险之间无显著关联。观察到TG单倍型与出血风险之间存在关联趋势，提示该单倍型对接受达比加群或阿哌沙班治疗的患者出血有保护作用。
