Personalizing Amlodipine Therapy in Hypertension The Role of Genetic Variants and Population-Specific Responses

Introduction: Amlodipine is a long-acting dihydropyridine calcium channel blocker used in hypertension management. Despite its widespread use, therapeutic response varies signifi cantly among individuals, infl uenced by genetic, environmental, and physiological factors. Pharmacogenomics, which studies genetic variation affecting drug responses, has identifi ed specifi c genetic variants associated with amlodipine metabolism and effi cacy. Genes such as CYP3A4, RYR3, CACNA1C, and CACNA1D are known to play a role in amlodipine’s pharmacokinetics and pharmacodynamics. This review examines these genetic variants and their impact on amlodipine effi cacy, with a focus on population-specifi c responses. Material and methods: This study utilized publicly available pharmacogenomic data from the PharmGKB and GTEx Portal to identify genetic variants associated with amlodipine effi cacy. Genetic variants from CYP3A4, RYR3, CACNA1C, and CACNA1D were selected based on their association with amlodipine response. Population-specifi c variations were also analyzed to assess differences in therapeutic outcomes across diverse biogeographical groups. Results: Seven single nucleotide polymorphisms (SNPs) from four genes were identifi ed: CYP3A4 (rs2246709, rs2740574), RYR3 (rs877087), CACNA1C (rs2239050, rs2239128), and CACNA1D (rs312481). SNPs such as rs2246709 in CYP3A4 and rs877087 in RYR3 were linked to enhanced amlodipine effi cacy in certain populations, while rs2740574 showed greater response in women. Variants like rs2239050 and rs312481 infl uenced amlodipine response in Central/South Asian and European populations. Conclusion: Genetic variants, including CYP3A4 (rs2246709, rs2740574), RYR3 (rs877087), CACNA1C (rs2239050, rs2239128), and CACNA1D (rs312481), signifi cantly infl uence amlodipine effi cacy in hypertensive patients. These fi ndings underscore the importance of genetic factors in personalizing hypertension treatment and optimizing drug effi cacy across diverse populations. However, further clinical validation and mechanistic studies are necessary to confi rm the therapeutic implications of these genetic associations. Understanding the distribution of these variants across populations may aid in tailoring amlodipine therapy based on ethnic and geographical factors, ensuring a more precise and effective treatment approach.