Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI:10.2147/PGPM.S481068
Asif Jan, Abdullah R Alanzi, Ramzi A Mothana, Jun-Ya Kaimori, Syed Shaukat Ali, Tahir Muhammad, Muhammad Saeed, Rani Akbar, Mehtab Khan
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Abstract

Introduction: Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes is a key area of focus in precision medicine. This study investigated the correlation between single nucleotide polymorphisms (SNPs) in selected genes (CACNA1C, CACNA1D, ABCB1, ACE, ADBR2, and NOS1AP) and the blood pressure (BP) control by amlodipine.

Methods: Four hundred individuals of Pashtun ethnicity undergoing amlodipine treatment for hypertension were included in the present study and divided into the controlled (BP less than 140/90 mmHg) and uncontrolled (BP greater than 140/90 mmHg) hypertension groups. Blood samples (3 mL) were collected from each participant, and DNA was extracted using the Kit method. Ten SNPs in amlodipine pharmacogenes were selected and genotyped using real-time PCR with the TaqMan® system. Logistic regression model was used to determine the association between SNPs and the amlodipine BP response.

Results: Notable association were observed between SNP rs2239050/CACNA1C and amlodipine blood pressure response, with GG genotype carriers demonstrating a better response (P=0.004) than individuals carrying CC or CG genotypes. SNP rs312481/CACNA1D also exhibited a positive pharmacogenetic association, Individuals with the GG genotype showing a considerable reduction in BP (P=0.021) compared to participants with AA or GA genotypes. In case of SNP rs429/ACE individuals carrying TA genotype were less likely to achieve BP control (P=0.002) than AA genotype carriers.

Conclusion: Our finding suggests that the SNPs rs2239050/CACNA1C, rs312481/CACNA1D and rs429/ACE influence amlodipine blood pressure response in patients with hypertension. It is recommended that prior knowledge of amlodipine associated pharmacogenetic variants is important that could improve its treatment outcomes in hypertensive patients.

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影响高血压患者氨氯地平血压反应的部分基因的药物基因组学研究
简介:尽管有各种降压药物,但不同个体对这些药物的反应却各不相同。了解个体基因变异如何影响药物治疗效果是精准医疗的一个重点领域。本研究调查了所选基因(CACNA1C、CACNA1D、ABCB1、ACE、ADBR2 和 NOS1AP)中的单核苷酸多态性(SNPs)与氨氯地平控制血压(BP)之间的相关性:本研究纳入了 400 名接受氨氯地平治疗的普什图族高血压患者,并将其分为高血压控制组(血压低于 140/90 mmHg)和未控制组(血压高于 140/90 mmHg)。研究人员采集了每位受试者的血液样本(3 mL),并采用试剂盒法提取了 DNA。筛选出氨氯地平药物基因中的 10 个 SNPs,并使用 TaqMan® 系统进行实时 PCR 基因分型。采用 Logistic 回归模型确定 SNP 与氨氯地平血压反应之间的关联:结果:SNP rs2239050/CACNA1C与氨氯地平血压反应之间存在显著关联,GG基因型携带者比CC或CG基因型携带者的反应更好(P=0.004)。SNP rs312481/CACNA1D 也显示出积极的药物遗传学关联,与 AA 或 GA 基因型的参与者相比,GG 基因型的个体显示出明显的血压下降(P=0.021)。就 SNP rs429/ACE 而言,与 AA 基因型携带者相比,TA 基因型携带者实现血压控制的可能性较小(P=0.002):我们的研究结果表明,SNPs rs2239050/CACNA1C、rs312481/CACNA1D 和 rs429/ACE 会影响高血压患者对氨氯地平的血压反应。建议事先了解与氨氯地平相关的药物基因变异,这对改善高血压患者的治疗效果非常重要。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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