摘要
目的 探讨基于基因多态性构建老年非瓣膜性心房颤动(non-valvular atrial fibrillation,NVAF)患者利伐沙班相关出血事件风险模型.方法 前瞻性选取2021年1月至2023年7月石河子大学第一附属医院全科医学科收治的老年NVAF患者268例,均使用利伐沙班治疗,根据随访观察12个月评估是否发生出血事件分为出血组47例和未出血组221例.比较2组患者临床资料、基因多态性,采用多因素logistic回归构建基于基因多态性的出血事件风险预测模型,并验证模型的效能.结果 出血组年龄明显高于未出血组,肌酐水平明显低于未出血组,差异有统计学意义(P＜0.01);出血组三磷酸腺苷结合盒亚家族B家族成员1(ATPbinding cassette,sub-family B mem-ber 1,ABCB1)基因rs1128503位点GG基因频率、rs4148738位点TT基因频率及细胞色素P450家族成员2C9(Cytochrome P450 2C9,CYP2C9)基因rs1057910位点AC基因频率显著低于未出血组(P＜0.05).多因素logistic回归显示,年龄(OR=1.136,95％CI:1.031～1.251),ABCB1 基因 rs1128503 位点 AA 型基因(OR=15.407,95％CI:4.259～55.741)、GA型基因(OR=6.990,95％CI:1.599～30.546)为老年NVAF患者利伐沙班相关出血事件风险的危险因素(P＜0.01);肌酐(OR=0.943,95％CI:0.899～0.989)、ABCB1 基因 rs4148738 位点 TT 型基因(OR=0.048,95％CI:0.009～0.242)、CYP2C9 基因 rs1057910 位点 AC 型基因(OR=0.092,95％CI:0.021～0.408)为老年NVAF患者利伐沙班相关出血事件风险的保护因素(P＜0.05).绘制ROC曲线显示,基于基因多态性构建的风险模型预测曲线下面积为0.827(95％CI:0.776～0.870),特异性为81.90％,敏感性为76.60％.结论 基于ABCB1基因、CYP2C9基因构建的老年NVAF患者利伐沙班相关出血事件风险模型具有较高的应用价值.
Abstract
Objective To establish a risk model of rivaroxaban-related bleeding events in elderly patients with non-valvular atrial fibrillation(NVAF)based on gene polymorphism.Methods A total of 268 elderly NVAF patients receiving rivaroxaban treatment in Department of General Practice of the First Affiliated Hospital of Shihezi University from January 2021 to July 2023 were enrolled in this study.According to whether bleeding events occurred in 12 months'follow-up,they were divided into a bleeding group(47 cases)and a non-bleeding group(221 cases).The clinical data and results of gene polymorphism were compared between the two groups.Multivari-ate logistic regression was adopted to construct a risk prediction model of bleeding events based on gene polymorphism,and the predictive performance was verified.Results Significantly ad-vanced age and lower creatinine level were observed in the bleeding group than the non-bleeding group(P＜0.01).The bleeding group had obviously lower GG genotype frequency at the rs1128503 locus and TT genotype frequency at the rs4148738 of ATP-binding cassette,sub-family B member 1(ABCB1),and lower AC genotype frequency at the rs1057910 locus of cytochrome P450 2C9(CYP2C9)than the non-bleeding group(P＜0.05).Multivariate logistic regression analy-sis showed that age(OR=1.136,95％CI:1.031-1.251),and AA genotype(OR=15.407,95％CI:4.259-55.741)and GA genotype(OR=6.990,95％CI:1.599-30.546)of ABCB1 rs1 128503 were risk factors for rivaroxaban-related bleeding events in elderly NVAF patients(P＜0.01).Creatinine(OR=0.943,95％CI:0.899-0.989),TT genotype at ABCB1 rs4148738(OR=0.048,95％CI:0.009-0.242)and AC genotype of CYP2C9 rs1057910(OR=0.092,95％CI:0.021-0.408)were protective factors for the risk(P＜0.05).ROC curve analysis indicated that the AUC value of the risk model based on gene polymorphism was 0.827(95％CI:0.776-0.870),the spe-cificity was 81.90％,and the sensitivity was 76.60％.Conclusion Our risk model of rivaroxaban-related bleeding events based on ABCB1 gene and CYP2C9 gene has high application value for elderly NVAF patients.
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