Garg Rajat, Saxena Sachin Kumar, Singh Vibha, Bashir Sabreen, Sharma Anuka, Sharma Varun
Department of Psychiatry, Military Hospital Kanpur Uttar Pradesh, India.
Department of Psychiatry, Command Hospital Bangalore, Karnataka, India.
Am J Transl Res. 2023 Jul 15;15(7):4763-4769. eCollection 2023.
Genetic variations contribute significantly to inter-individual responses to drugs and side effects. Pharmacogenomics has the potential to be utilized as a tool in disorders like schizophrenia with a high degree of genetic inheritance, although data on pharmacogenomics of schizophrenia are limited. Olanzapine and risperidone are the frequently used anti-psychotic drugs used in clinics. Studies have observed the variability in the response of both drugs in schizophrenic individuals. Considering the pharmacogenomics importance of both drugs, we aim to examine the cytochrome P 4501A1 (CYP1A1) and regulator of G-protein signaling 4 (RGS4) variants and their metabolizing status in 94 schizophrenic individuals of Indian descent.
The present study is retrospective observational study. The metabolizing status of schizophrenic individuals was examined using Axiom Precision Medicine Diversity Array (PMDA) and the data were analyzed with the help of SNP Axiom Analysis Suite v5.1 (Affymetrix). The pharmacogenomics annotation was performed using PharmGKB.
Genotype and allele frequencies were observed. The results reveal the high frequency of poor metabolizers of olanzapine and risperidone in the studied cohort. In lieu of the high distribution of poor metabolizers, we compare observed allele frequencies with global populations' data to understand the variability of the genetic pool attained by Indian schizophrenic individuals.
Interestingly, the Indian schizophrenic cohort forms a different cluster compared to global populations, suggesting that pharmacogenomics testing might play an important role in clinical decision making for schizophrenia drug management.
基因变异对个体对药物的反应及副作用有显著影响。药物基因组学有潜力作为一种工具应用于精神分裂症等具有高度遗传倾向的疾病，尽管关于精神分裂症药物基因组学的数据有限。奥氮平和利培酮是临床上常用的抗精神病药物。研究观察到这两种药物在精神分裂症患者中的反应存在变异性。鉴于这两种药物的药物基因组学重要性，我们旨在研究94名印度裔精神分裂症患者中细胞色素P4501A1（CYP1A1）和G蛋白信号调节剂4（RGS4）变体及其代谢状态。
本研究为回顾性观察研究。使用Axiom精密医学多样性阵列（PMDA）检测精神分裂症患者的代谢状态，并借助SNP Axiom分析套件v5.1（Affymetrix）对数据进行分析。使用PharmGKB进行药物基因组学注释。
观察到基因型和等位基因频率。结果显示，在所研究的队列中，奥氮平和利培酮的代谢不良者频率较高。鉴于代谢不良者的高比例分布，我们将观察到的等位基因频率与全球人群的数据进行比较，以了解印度精神分裂症患者基因库的变异性。
有趣的是，与全球人群相比，印度精神分裂症队列形成了一个不同的聚类，这表明药物基因组学检测可能在精神分裂症药物管理的临床决策中发挥重要作用。
