Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif

Introduction<p>Genetic polymorphisms in CYP2D6 and CYP2C19 significantly influence the metabolism, efficacy, and safety of antidepressant medications. Limited data exist on the prevalence of these actionable pharmacogenetic variants in the Central Indian population. This study aimed to determi...

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Autore principale: Santenna Chenchula (14775163) (author)
Altri autori: Atal Shubham (22679330) (author), Rozatkar Abhijit (22679333) (author), Tamonud Modak (22679336) (author), Kohat Komal (22679339) (author), Ratinder Jhaj (22679342) (author), Singh Jitendra (22679345) (author), Satyaprakash V. (22679348) (author), Sadasivam Balakrishnan (22679351) (author)
Pubblicazione: 2025
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_version_ 1849927635647332352
author Santenna Chenchula (14775163)
author2 Atal Shubham (22679330)
Rozatkar Abhijit (22679333)
Tamonud Modak (22679336)
Kohat Komal (22679339)
Ratinder Jhaj (22679342)
Singh Jitendra (22679345)
Satyaprakash V. (22679348)
Sadasivam Balakrishnan (22679351)
author2_role author
author
author
author
author
author
author
author
author_facet Santenna Chenchula (14775163)
Atal Shubham (22679330)
Rozatkar Abhijit (22679333)
Tamonud Modak (22679336)
Kohat Komal (22679339)
Ratinder Jhaj (22679342)
Singh Jitendra (22679345)
Satyaprakash V. (22679348)
Sadasivam Balakrishnan (22679351)
author_role author
dc.creator.none.fl_str_mv Santenna Chenchula (14775163)
Atal Shubham (22679330)
Rozatkar Abhijit (22679333)
Tamonud Modak (22679336)
Kohat Komal (22679339)
Ratinder Jhaj (22679342)
Singh Jitendra (22679345)
Satyaprakash V. (22679348)
Sadasivam Balakrishnan (22679351)
dc.date.none.fl_str_mv 2025-11-25T06:25:15Z
dc.identifier.none.fl_str_mv 10.3389/fphar.2025.1697866.s001
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/Image_2_Pharmacogenetic_variations_and_clinical_implications_of_actionable_CYP2D6_CYP2C19_variants_in_Central_Indian_patients_with_common_mental_disorders_tif/30704159
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Pharmacology
pharmacogenetics
CYP2D6
CYP2C19
antidepressants
common mental disorders
indian population
copy number variation
CPIC
dc.title.none.fl_str_mv Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description Introduction<p>Genetic polymorphisms in CYP2D6 and CYP2C19 significantly influence the metabolism, efficacy, and safety of antidepressant medications. Limited data exist on the prevalence of these actionable pharmacogenetic variants in the Central Indian population. This study aimed to determine the frequency of clinically actionable Tier-1 alleles, genotypes, and metabolizer phenotypes and to evaluate their clinical relevance in patients with common mental disorders (CMDs).</p>Methods<p>A total of 509 adults diagnosed with depression and anxiety disorders and receiving SSRI & SNRI antidepressant therapy were enrolled from the Department of Psychiatry, AIIMS Bhopal. Genotyping was performed using the KASP qPCR assay, and CYP2D6 copy number variations (CNVs) were determined using the TaqMan qPCR assay.</p>Results<p>Among the Central Indian cohort, the most frequent CYP2D6 alleles were *10 (21.6%), *41 (17.3%), and *4 (10.4%), while *3 (5.7%), *6 (1.9%). CNVs, Gene deletions(*5) and Gene duplications(xN) were detected in 4.2% and 4.1% of the cohort. For CYP2C19, the *2 (37.3%), *3 (2.3%), and *17 (16.1%) alleles were observed. Non-normal metabolizer phenotypes were present in 46.2% for CYP2D6 and 74.2% for CYP2C19; CYP2D6 ultra-rapid metabolizers accounted for 5.3%. Overall, 86% of participants had at least one clinically actionable pharmacogenetic phenotype. Overall, 7.5% of patients carried CYP2D6 variants and 20.6% carried CYP2C19 variants, for which CPIC guidelines recommend alternative drug selection or dose modification.</p>Discussion<p>This study demonstrates a high prevalence of actionable CYP2D6 and CYP2C19 variants in the Central Indian population, underscoring the need for pharmacogenetic integration in psychiatric prescribing in Indian clinical settings, to enhance treatment efficacy and minimize adverse events.</p>
eu_rights_str_mv openAccess
id Manara_0c62d0cf2e403d2696b3f08a1a0ad93b
identifier_str_mv 10.3389/fphar.2025.1697866.s001
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/30704159
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tifSantenna Chenchula (14775163)Atal Shubham (22679330)Rozatkar Abhijit (22679333)Tamonud Modak (22679336)Kohat Komal (22679339)Ratinder Jhaj (22679342)Singh Jitendra (22679345)Satyaprakash V. (22679348)Sadasivam Balakrishnan (22679351)PharmacologypharmacogeneticsCYP2D6CYP2C19antidepressantscommon mental disordersindian populationcopy number variationCPICIntroduction<p>Genetic polymorphisms in CYP2D6 and CYP2C19 significantly influence the metabolism, efficacy, and safety of antidepressant medications. Limited data exist on the prevalence of these actionable pharmacogenetic variants in the Central Indian population. This study aimed to determine the frequency of clinically actionable Tier-1 alleles, genotypes, and metabolizer phenotypes and to evaluate their clinical relevance in patients with common mental disorders (CMDs).</p>Methods<p>A total of 509 adults diagnosed with depression and anxiety disorders and receiving SSRI & SNRI antidepressant therapy were enrolled from the Department of Psychiatry, AIIMS Bhopal. Genotyping was performed using the KASP qPCR assay, and CYP2D6 copy number variations (CNVs) were determined using the TaqMan qPCR assay.</p>Results<p>Among the Central Indian cohort, the most frequent CYP2D6 alleles were *10 (21.6%), *41 (17.3%), and *4 (10.4%), while *3 (5.7%), *6 (1.9%). CNVs, Gene deletions(*5) and Gene duplications(xN) were detected in 4.2% and 4.1% of the cohort. For CYP2C19, the *2 (37.3%), *3 (2.3%), and *17 (16.1%) alleles were observed. Non-normal metabolizer phenotypes were present in 46.2% for CYP2D6 and 74.2% for CYP2C19; CYP2D6 ultra-rapid metabolizers accounted for 5.3%. Overall, 86% of participants had at least one clinically actionable pharmacogenetic phenotype. Overall, 7.5% of patients carried CYP2D6 variants and 20.6% carried CYP2C19 variants, for which CPIC guidelines recommend alternative drug selection or dose modification.</p>Discussion<p>This study demonstrates a high prevalence of actionable CYP2D6 and CYP2C19 variants in the Central Indian population, underscoring the need for pharmacogenetic integration in psychiatric prescribing in Indian clinical settings, to enhance treatment efficacy and minimize adverse events.</p>2025-11-25T06:25:15ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fphar.2025.1697866.s001https://figshare.com/articles/figure/Image_2_Pharmacogenetic_variations_and_clinical_implications_of_actionable_CYP2D6_CYP2C19_variants_in_Central_Indian_patients_with_common_mental_disorders_tif/30704159CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307041592025-11-25T06:25:15Z
spellingShingle Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
Santenna Chenchula (14775163)
Pharmacology
pharmacogenetics
CYP2D6
CYP2C19
antidepressants
common mental disorders
indian population
copy number variation
CPIC
status_str publishedVersion
title Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
title_full Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
title_fullStr Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
title_full_unstemmed Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
title_short Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
title_sort Image 2_Pharmacogenetic variations and clinical implications of actionable CYP2D6/CYP2C19 variants in Central Indian patients with common mental disorders.tif
topic Pharmacology
pharmacogenetics
CYP2D6
CYP2C19
antidepressants
common mental disorders
indian population
copy number variation
CPIC