高血压患者中影响氨氯地平血压反应的选定基因的药物基因组学研究。

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

作者信息

Jan Asif, Alanzi Abdullah R, Mothana Ramzi A, Kaimori Jun-Ya, Ali Syed Shaukat, Muhammad Tahir, Saeed Muhammad, Akbar Rani, Khan Mehtab

机构信息

Department of Pharmacy, University of Peshawar, Peshawar, 25000, Pakistan.

District Headquarter Hospital (DHQH) Charsadda, Charsadda, 24430, Pakistan.

出版信息

Pharmgenomics Pers Med. 2024 Oct 29;17:473-486. doi: 10.2147/PGPM.S481068. eCollection 2024.

DOI:10.2147/PGPM.S481068

PMID:39492848

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11531276/

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.

摘要

引言

尽管有多种抗高血压药物可供使用，但个体对这些药物的反应各不相同。了解个体基因变异如何影响药物治疗效果是精准医学的一个关键重点领域。本研究调查了选定基因（CACNA1C、CACNA1D、ABCB1、ACE、ADBR2和NOS1AP）中的单核苷酸多态性（SNP）与氨氯地平控制血压（BP）之间的相关性。

方法

本研究纳入了400名接受氨氯地平治疗高血压的普什图族个体，并将其分为血压控制组（血压低于140/90 mmHg）和未控制组（血压高于140/90 mmHg）高血压组。从每位参与者采集3 mL血样，并使用试剂盒方法提取DNA。选择氨氯地平药物代谢基因中的10个SNP，并使用TaqMan系统通过实时PCR进行基因分型。采用逻辑回归模型确定SNP与氨氯地平血压反应之间的关联。

结果

观察到SNP rs2239050/CACNA1C与氨氯地平血压反应之间存在显著关联，GG基因型携带者的反应（P = 0.004）优于携带CC或CG基因型的个体。SNP rs312481/CACNA1D也表现出正向药物遗传学关联，与AA或GA基因型参与者相比，GG基因型个体的血压显著降低（P = 0.021）。对于SNP rs429/ACE，携带TA基因型的个体比AA基因型携带者更难实现血压控制（P = 0.002）。