老年心房颤动患者基因的单核苷酸多态性与利伐沙班血浆谷浓度的相关性研究

Correlation between SNP and plasma trough concentration of rivaroxaban in elderly patients with atrial fibrillation

目的观察老年心房颤动患者基因的单核苷酸多态性(SNP)对利伐沙班谷浓度的影响。方法选择2020年4月至2021年9月解放军总医院第二医学中心就诊的老年心房颤动患者113例。测定7个SNP及利伐沙班谷浓度,分析利伐沙班谷浓度/剂量(C0 h/D)与临床指标的相关性及不同基因型C0 h/D的差异。结果相关性分析显示,利伐沙班谷浓度与剂量呈正相关(r=0.294,P=0.002),与年龄呈负相关(r=-0.291,P=0.002);C0 h/D与凝血酶原时间呈正相关(r=0.205,P=0.029),与eGFR呈负相关(r=-0.252,P=0.007)。ABCB1 rs1128503 AA、AG和GG型患者利伐沙班C0 h/D比较,差异有统计学意义(P=0.011)。ABCB1 rs1128503 AG和GG型患者利伐沙班C0 h/D明显高于AA型患者[6.29(3.61,17.71)ng/(ml·mg)、9.20(3.53,29.34)ng/(ml·mg)vs 3.65(1.18,7.90)ng/(ml·mg),P<0.05]。结论ABCB1基因遗传变异可能对老年心房颤动患者利伐沙班血浆浓度个体差异造成影响。

Objective To observe the effect of single nucleotide polymorphisms(SNP)on the plasma trough concentration of rivaroxaban in elderly patients with atrial fibrillation(AF).Methods A total of 113 elderly AF patients who attended the Second Medical Center of Chinese PLA General Hospital from April 2020 to September 2021 were enrolled.Seven SNP and plasma trough concentrations of rivaroxaban were detected.The correlation between rivaroxaban trough concentration/dose(C_(0 h)/D)and clinical indicators was analyzed,and the differences in rivaroxaban C_(0 h)/D in different genotypes were analyzed.Results Correlation analysis showed that rivaroxaban trough concentration was positively correlated with its dose(r=0.294,P=0.002)and negatively with age(r=-0.291,P=0.002).Rivaroxaban C_(0 h)/D was positively correlated with prothrom-bin time(r=0.205,P=0.029)and negatively correlated with eGFR(r=-0.252,P=0.007).There were statistical differences in rivaroxaban C_(0 h)/D in ABCB1 rs1128503 AA,AG and GG genotypes(P=0.011).The patients carrying AG and GG genotypes had significantly higher C_(0 h)/D than those of AA genotype[6.29(3.61,17.71)ng/(ml·mg)and 9.20(3.53,29.34)ng/(ml·mg)vs 3.65(1.18,7.90)ng/(ml·mg),P<0.05].Conclusion ABCB1 genetic variation may cause the individual difference of plasma trough concentration of rivaroxaban in elderly AF patients.