服用硝苯地平原发性高血压患者的药物基因组学研究

Pharmacogenomic Study of Primary Hypertensive Patients Taking Nifedipine

目的基于药物基因组学技术,分析服用硝苯地平原发性高血压患者药物相关基因多态性分布情况,评估基因导向使用硝苯地平的应用价值。方法选取2021年10月至2023年10月收治的485例服用硝苯地平的原发性高血压患者作为研究对象,分析硝苯地平药物相关基因,并进一步分析各基因多态性位点基因型分布情况,比较不同疗效、有无下肢水肿患者各基因多态性位点基因型分布情况,行单因素、多因素Logistic回归分析基因多态性位点与疗效、下肢水肿的关系。结果细胞色素P450(CYP)3A5*3 A6986、尿素转运型糖蛋白A2抗体(SLC14A2)rs1123617、SLC14A2 rs3745009、CYP3A4 rs2242480、肾上腺素能α_(1)A受体(ADRA1A)rs1048101、肾上腺素能β1受体(ADRB1)c.1165、肾上腺素能β2受体(ADRB2)rs1042713、血管紧张素转换酶(ACE)rs4646994基因多态性均符合Hardy-Weinberg平衡定律,说明样本具有代表性。不同疗效、有无下肢水肿患者CYP3A5*3 A6986、CYP3A4 rs2242480、ADRB1 c.1165、ADRB2 rs1042713、ACE rs4646994位点基因型比较,差异有统计学意义(P<0.05,P<0.01);而SLC14A2 rs1123617、SLC14A2 rs3745009、ADRA1A rs1048101位点基因型比较无统计学差异(P>0.05)。单因素、多因素Logistic回归分析显示,CYP3A5*3 A6986 G>A、CYP3A4 rs2242480 C>T、ADRB1 c.1165 C>G、ADRB2 rs1042713 G>A、ACE rs4646994 I>D与服用硝苯地平原发性高血压患者疗效、下肢水肿显著相关(P<0.01)。结论服用硝苯地平原发性高血压患者药物相关基因多态性与疗效、下肢水肿密切相关,可为临床医师制订个性化治疗方案提供参考。

Objective To analyze the distribution of drug-related gene polymorphism in primary hypertensive patients taking Nifedipine based on pharmacogenomics technology,and to evaluate the application value of gene-directed use of Nifedipine.Methods A total of 485 patients with primary hypertension who took Nifedipine from October 2021 to October 2023 were selected as research subjects,to analyze Nifedipine drug-related genes,further analyze the genotype distribution of each gene polymorphism site,and compare the genotype distribution of each gene polymorphism site in patients with different therapeutic effects and with or without lower limb edema.Univariate and multivariate Logistic regression analyses were performed to analyze the relationship of gene polymorphic loci with therapeutic effect and lower limb edema.Results Cytochrome P450(CYP)3A5*3 A6986G,urea-transporter glycoprotein A2 antibody(SLC14A2)rs1123617,SLC14A2 rs3745009,CYP3A4 rs2242480,adrenergicα_(1)A receptor(ADRA1A)rs1048101,adrenergicβ1 receptor(ADRB1)c.1165,adrenergicβ2 receptor(ADRB2)rs1042713 and angiotensin converting enzyme(ACE)rs4646994 polymorphisms were consistent with the Hardy-weinberg equilibrium law,suggesting that the samples were representative.The genotypes of CYP3A5*3 A6986,CYP3A4 rs2242480,ADRB1 c.1165,ADRB2 rs1042713 and ACE rs4646994 in patients with different therapeutic effects and with or without lower limb edema were statistically significant(P<0.05,P<0.01),while there were no significant difference in genotype comparison between SLC14A2 rs1123617,SLC14A2 rs3745009,and ADRA1A rs1048101 loci(P>0.05).Univariate and multivariate Logistic regression analyses showed that CYP3A5*3 A6986 G>A,CYP3A4 rs2242480 C>T,ADRB1 c.1165 C>G,ADRB2 rs1042713 G>A,and ACE rs4646994 I>D were significantly correlated with the efficacy and lower limb edema of primary hypertensive patients taking Nifedipine(P<0.01).Conclusion Drug-related gene polymorphism in primary hypertensive patients taking Nifedipine is closely related to efficacy and lower limb edema,which can provide reference for clinicians to make personalized treatment plan.