Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.
Pediatric Oncology and Hematology, CANSEARCH Research Platform in Pediatric Oncology and Hematology, University of Geneva, Geneva, Switzerland.
Indian J Pharmacol. 2024 Jul 1;56(4):277-284. doi: 10.4103/ijp.ijp_198_24. Epub 2024 Sep 10.
Proton-pump inhibitors (PPIs) are widely prescribed to decrease stomach acid and treat various acid-related Gastrointestinal tract (GIT) diseases. However, genetic variations, particularly in the CYP2C19 gene, affect PPIs metabolism and efficacy. Variants in CYP2C19 can result in different rates of PPI metabolism, influencing their effectiveness. Personalized medicine strategies, such as genotyping for CYP2C19, have the potential to enhance the effectiveness of PPI therapy and patient safety. This review aims to describe the relevance of CYP2C19 genetic profiling in the indian population, including normal function (e.g. CYP2C19*1, *11, *13, *15, *18, 28, and 38), decreased function (e.g., CYP2C199, *10, *16, *19, 25, and 26), loss of function (e.g., CYP2C192, *3, *4, *5, *6, *7, *8, *22, *24, *35, *36, and 37), and increased function (e.g., CYP2C1917) variants. This review also examines the clinical pharmacogenomics implementation consortium (CPIC)-CYP2C19-PPI guidelines to highlight the importance of pharmacogenomics (PGx)-informed personalized PPI therapy for gastroesophageal reflux disease and peptic ulcer disease treatment. On average, each person in India possesses eight pharmacogenetic (PGx) variants that can be clinically significant, underscoring the need for preemptive testing. Implementing CYP2C19 genetic testing in India requires expanding laboratory capacity, increasing accessibility in primary care, increasing public awareness, collaboration between pharmacovigilance and PGx programs, investing in advanced sequencing technologies, data management systems, and integration with electronic health records and clinical decision support systems. Addressing challenges such as genetic diversity, socioeconomic factors, health-care access issues, and shortage of trained professionals is essential for implementation. Due to the lack of definitive country-specific policies and PGx guidelines from Indian drug regulatory agencies, guidelines from international consortia such as the Clinical Pharmacogenetics Implementation Consortium and drug labeling offer crucial foundational evidence. This evidence can be used to enhance patient outcomes and ensure the safe and effective use of PPIs in India.
质子泵抑制剂（PPIs）被广泛用于减少胃酸并治疗各种酸相关的胃肠道（GIT）疾病。然而，遗传变异，特别是 CYP2C19 基因的变异，会影响 PPI 的代谢和疗效。CYP2C19 的变异会导致 PPI 代谢的不同速率，从而影响其疗效。个性化医疗策略，如 CYP2C19 的基因分型，有可能提高 PPI 治疗的效果和患者的安全性。本综述旨在描述 CYP2C19 基因谱在印度人群中的相关性，包括正常功能（如 CYP2C19*1、*11、*13、*15、*18、28 和 38）、功能降低（如 CYP2C199、*10、*16、*19、25 和 26）、功能丧失（如 CYP2C192、*3、*4、*5、*6、*7、*8、*22、*24、35、36 和37）和功能增强（如 CYP2C1917）变体。本综述还检查了临床药物基因组学实施联盟（CPIC）-CYP2C19-PPI 指南，以强调药物基因组学（PGx）指导下的个体化 PPI 治疗在胃食管反流病和消化性溃疡病治疗中的重要性。平均而言，印度每个人都拥有八种可能具有临床意义的药物遗传学（PGx）变异，这突显了进行预防性检测的必要性。在印度实施 CYP2C19 基因检测需要扩大实验室能力，增加初级保健中的可及性，提高公众意识，在药物警戒和 PGx 计划之间建立合作关系，投资于先进的测序技术、数据管理系统，并将其与电子健康记录和临床决策支持系统集成。解决遗传多样性、社会经济因素、医疗保健获取问题和缺乏训练有素的专业人员等挑战至关重要。由于印度药品监管机构缺乏明确的国家特定政策和 PGx 指南，国际联盟（如临床药物基因组学实施联盟）和药品标签的指南提供了至关重要的基础证据。该证据可用于改善患者的预后并确保 PPI 在印度的安全有效使用。
