高血压患者药物基因组学特征分析及基因导向治疗的研究OA

Objective To investigate the distribution patterns of pharmacogenomic characteristics in hypertensive patients treated and to evaluate the differential benefits of genotype-guided therapy in calcium channel blocker(CCB)strategy versus beta-blocker strategy.Methods In the first phase,pharmacogenomic data of patients with primary hypertension treated at our hospital were analyzed.In the second phase,treatment-naive hypertensive patients were enrolled and randomly assigned in a 1∶1∶1∶1 ratio to four groups:genotype-guided CCB strategy,standard CCB strategy,genotype-guided beta-blocker strategy,and standard beta-blocker strategy.Seven key pharmacogenomic loci,including adrenergic beta-1 receptor(ADRB1)rs1801253(1165G＞C)and cytochrome P450 3A5(CYP3A5)rs776746,were genotyped using polymerase chain reaction(PCR)-melting curve method.Primary outcomes included time to blood pressure control,incidence of treatment-related adverse events(TRAEs),and length of hospital stay.Results In the retrospective phase,2 783 patients were enrolled.The C allele frequency of ADRB1 rs1801253 was 76.02％(4 231 cases/5 566 cases),and the G allele frequency of CYP3A5*3 was 72.97％(4 062 cases/5 566 cases).In the prospective phase,300 patients were enrolled.The genotype-guided therapy significantly shortened time to blood pressure control(mean difference:-2.10 days,95％confidence interval(CI):-2.80 to-1.40,P＜0.001),with a significant interaction between therapy approach and treatment strategy(P＜0.05).Specifically,in the CCB strategy,genotype-guided therapy reduced control time by 3.20 days(95％CI:-4.10 to-2.30)versus standard therapy,whereas in the beta-blocker strategy,the reduction was only 0.90 days(95％CI:-1.70 to-0.10).Genotype-guided therapy also significantly lowered TRAEs incidence[12.67％(19 cases/150 cases)vs.25.33％(38 cases/150 cases),P＜0.001].Conclusion Hypertensive patients at our hospital exhibited a distinct pharmacogenomic profile.Genotype-guided therapy demonstrates substantially greater clinical benefits when applied to CCB strategy than to beta-blocker strategy,providing robust evidence for precision hypertension management within this single-center clinical setting.