Molecular docking analysis of CYP2C19 gene polymorphisms and their effect on escitalopram plasma concentrations in major depressive disorders patients

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2024-12-13 DOI:10.1016/j.genrep.2024.102119

B. Jeevan Kumar , Vijayakumar Thangavel Mahalingam , M. Ganesh Kumar , S. Mohana Lakshmi

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引用次数: 0

Abstract

Background

Among depressed patients, escitalopram plasma levels differed between those who were considered extensive metabolizers and inadequate metabolizers of CYP2C19. Consequently, we studied the impact of CYP2C19 gene variants on the levels of drugs in the bloodstream of individuals suffering from MDD (Major Depressive Disorder) in south India.

Heterocyclic-based drugs have strong bioactivities and are active pharmacophores, used to design several drugs.

Methods

A total of 109 individuals with MDD who prescribed escitalopram at doses of were 5, 10, 15, or 20 mg daily participated in this research. High-performance liquid chromatography (HPLC) was used to analyze the level of escitalopram in blood. The polymorphisms of the CYP2C19 were determined by employing the PCR techniques. The molecular docking analysis of escitalopram against different proteins responsible for SIRT6 (PDB ID: 5Y2F), OSR1 kinase (PDB ID: 2VWI), Akt1 (PDB ID: 7APJ) & desvenlafaxine (PDB ID: 4MMC) is discussed.

Results

Our study found that 55 % of the subjects were intermediate metabolizers, followed by extensive (19.3 %), poor (17.4 %), and ultra-rapid (8.3 %). A significant correlation is identified between the steady state plasma concentration and Sex with (P- Value <0.05), and an insignificant correlation was seen in Age and BMI with (P – Value >0.05). Most gene variants seen in the study population were CYP2C19*1/*2, accounting for 49 individuals (44.9 %). Many heterocyclic-based derivatives show residual interactions, affinity, and hydrogen bonding with the different proteins with escitalopram, which were identified by investigating such heterocyclic compounds in silico molecular docking analysis. The research presented here showed that heterocyclic derivatives may operate as potent anti-ischemic agents when combined with other compounds to produce highly efficient anti-ischemic agents.

Conclusion

These findings showed that sex substantially impacted the CYP2C19 genetic variation. Medication administration to individuals with CYP2C19 PM (poor metabolizers) requires special caution.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.