Post-treatment symptomatic improvement of the eastern Indian ADHD probands is influenced by CYP2D6 genetic variations.

Q2 Pharmacology, Toxicology and Pharmaceutics Drug metabolism and personalized therapy Pub Date : 2023-03-01 DOI:10.1515/dmpt-2022-0120

Mahasweta Chatterjee, Sharmistha Saha, Subhamita Maitra, Anirban Ray, Swagata Sinha, Kanchan Mukhopadhyay

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引用次数: 2

Abstract

Objectives: Symptomatic remediation from attention deficit hyperactivity disorder (ADHD)-associated traits is achieved by treatment with methylphenidate (MPH)/atomoxetine (ATX). We have analyzed the association of functional CYP2D6 variations, rs1065852, rs3892097, rs1135840, and rs1058164, with ADHD in the Indian subjects.

Methods: Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders. Trait scores were obtained from the Conner's Parents Rating Scale-Revised. After obtaining informed consent, blood was collected for DNA isolation, and genotyping was performed by PCR or TaqMan-based methods. Probands were treated with MPH or ATX based on age, symptoms, and drug availability. Treatment outcome was assessed using a structured questionnaire. Data obtained was analyzed to identify the association of CYP2D6 variations and the SLC6A3 rs28363170 with the treatment outcome.

Results: The frequency of rs1135840 "G" and rs1065852 "G" was higher in the male ADHD probands. Bias in parental transmission (p=0.007) and association with higher trait scores were observed for rs1065852 "A". Independent influence of rs1065852 on ADHD was also observed. Probands carrying rs1065852 'GG', rs1135840 'CG', and rs28363170 10R exhibited significant symptomatic improvement with MPH, while probands with rs1135840 'CC' and rs28363170 9R showed improvement after ATX treatment.

Conclusions: ADHD probands having specific CYP2D6 genetic variations respond differentially to pharmaceutical intervention.

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东印度ADHD先证者的治疗后症状改善受CYP2D6基因变异的影响。

目的:通过哌醋甲酯(MPH)/阿托西汀(ATX)治疗，可实现对注意缺陷多动障碍(ADHD)相关特征的症状性补救。我们分析了功能性CYP2D6变异rs1065852、rs3892097、rs1135840和rs1058164与印度受试者ADHD的关系。方法:按照《精神障碍诊断与统计手册》招募受试者。特质得分来自康纳父母评定量表-修订版。在征得知情同意后，采集血样进行DNA分离，采用PCR或taqman法进行基因分型。先证者根据年龄、症状和药物可用性接受MPH或ATX治疗。采用结构化问卷对治疗结果进行评估。对获得的数据进行分析，以确定CYP2D6变异和SLC6A3 rs28363170与治疗结果的关系。结果:男性ADHD先证者中rs1135840“G”和rs1065852“G”的频率较高。rs1065852“A”存在亲本遗传偏倚(p=0.007)和与较高性状得分相关。rs1065852对ADHD的独立影响也被观察到。携带rs1065852 'GG'、rs1135840 'CG'和rs28363170 10R的先证者在MPH治疗后症状得到显著改善，而携带rs1135840 'CC'和rs28363170 9R的先证者在ATX治疗后症状得到改善。结论:具有特定CYP2D6基因变异的ADHD先证者对药物干预的反应不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.