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The Influence of CYP2C19 Gene Polymorphism on Selective Serotonin Reuptake Inhibitors In Patients with Major Depressive Disorder: A Pharmacogenetic Prospecting Approach Urbaningrum, Lestari Mahardika; Hermosaningtyas, Anastasia Aliesa; Kasasiah, Ahsanal; Rahmasari, Ratika; Raekiansyah, Muhareva; Hartanto, Adrian; Malau, Jekmal
Journal of Biomedicine and Translational Research Vol 10, No 1 (2024): April 2024
Publisher : Faculty of Medicine, Universitas Diponegoro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14710/jbtr.v10i1.20338

Major Depressive Disorder (MDD) is a chronic disorder characterized by at least a two-week-long major depressive episode. Selective Serotonin Reuptake Inhibitors (SSRIs) remain the primary prescribed antidepressants to treat MDD. However, SSRIs themselves are found to be ineffective in some individuals or may even lead to adverse side effects. These variable responses have been linked to the drug being metabolized by CYP2C19, which exhibited various polymorphisms. Understanding how gene polymorphism affects drug metabolism is essential since these insights can revolutionize clinical practice, allowing for more precise and personalized treatment approaches that optimize efficacy while minimizing side effects. This issue is particularly pertinent in Indonesia, where research in this area lags behind the pressing need for such studies. In this review, the impact of CYP2C19 polymorphism on the effectiveness of SSRI class drugs, namely citalopram, escitalopram, and sertraline, are explored. Nine relevant articles related to the topic have been studied in Japan, China, Turkey, Russia, Scandinavia, and Australia. The results concluded that CYP2C19 polymorphism can influence the metabolism of SSRIs (citalopram, escitalopram, and sertraline) due to its variability in enzyme activities, which includes both loss-of-function (*2, *3) and gain-of-function (*17) polymorphisms. Consequently, these genetic variations can lead to significant changes in drug efficacy and safety changes within individual patients. This review sheds light on the importance of considering genetic factors when prescribing SSRIs for MDD in the future treatment strategies.

Engineering of LysR-type Regulator DmlR in Burkholderia ubonensis CP01 to Enhance Its Antifungal Production against Ganoderma boninense Budinarta, Widyah; Purnamasari, Maria Indah; Hermosaningtyas, Anastasia Aliesa; Arifudin Rafif , Muhammad Ghildan; Prihatna , Cahya; Suwanto, Antonius
HAYATI Journal of Biosciences Vol. 33 No. 1 (2026): January 2026
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.4308/hjb.33.1.28-43

The utilization of an antifungal substance, occidiofungin and burkholdine, derived from Burkholderia ubonensis CP01 has displayed promising results in the management of basal stem rot caused by Ganoderma boninense. The study aims to further enhance the antifungal production of B. ubonensis CP01 through genetic modification. Through comparative genetic analysis, we identified the dmlR gene in B. ubonensis CP01, which is homologous to the scmR gene, a LysR-type transcriptional regulator (LTTR), in B. thailandensis. Deleting the dmlR gene in CP01 resulted in a complete loss of antifungal synthesis. In contrast, overexpression of this gene led to a substantial increase in antifungal production, as determined by an agar well diffusion assay. These findings suggest that dmlR acts as a positive regulator of antifungal gene expression in B. ubonensis CP01. RP-HPLC analysis revealed that the mutant strain overexpressing the dmlR gene (mutant WB12) produced a higher peak at the 24-25 minute elution time. Previous high-resolution mass spectrometry analysis by our group identified the compound at this peak as six analog compounds with monoisotopic masses similar to those of cyclic lipopeptides, including occidiofungin and burkholdine. The WB12 mutant exhibited approximately 15% higher concentrations of antifungal compounds than the wild type. Additionally, whole genome sequencing confirmed that the introduced dmlR gene had been integrated into the locus on chromosome 2 of B. ubonensis CP01. LTTRs play a pivotal role in regulating the production of antifungal agents in CP01. Furthermore, it highlights the potential for manipulating LTTRs to enhance the desirable characteristics of the Burkholderia genus in regard to the production of secondary metabolites.

DEVELOPMENT OF PLASMID-BASED FOR EXTERNAL CONTROL MATERIALS OF CYP2D6*10 (rs1065852) GENE PCR-BASED DETECTION Malau, Jekmal; Zahra, Aliya Azkia; Kasasiah, Ahsanal; Rahmasari, Ratika; Raekiansyah, Muhareva; Rohmah, Siti; Meilani, Nanda Diva; Septi, Annisa Frastica; Zahro, Aurora Fatimatuz; Annajla, Fathina; Hermosaningtyas, Anastasia Aliesa; Hilmi, Indah Laily
Jurnal Bioteknologi & Biosains Indonesia (JBBI) Vol. 10 No. 2 (2023)
Publisher : BRIN - Badan Riset dan Inovasi Nasional

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55981/jbbi.2023.2557

Reliable clinical diagnosis of Single Nucleotide Polymorphisms (SNPs) is necessary for personalizing tamoxifen medication according to CYP2D6*10 genetic variations. Our research aimed to create a recombinant plasmid for external control material with a molecular size of 3812 bp. The recombinant plasmid was achieved by cloning an 838 bp gene insert of CYP2D6*10 rs1065852 into a 2974 bp pJET1.2 plasmid into Escherichia coli DH10B and selection on ampicillin agar medium. Isolated E. coli recombinants provided the plasmid molecules for analysis. Bi-directional sequencing and Real-Time PCR confirmed the presence of wild-type and mutant rs1065852 DNA fragments in the plasmid, namely homozygote CC and TT. The conclusion is that we have successfully introduced a novel recombinant plasmid developed by cloning the SNP rs1065852, which carries the 100C>T mutation, using pJET 1.2/blunt system, which could significantly enhance the accuracy of clinical SNP diagnostics for personalized medicine in breast cancer treatment.

DEVELOPMENT OF PLASMID-BASED FOR EXTERNAL CONTROL MATERIALS OF CYP2D6*10 (rs1065852) GENE PCR-BASED DETECTION Malau, Jekmal; Zahra, Aliya Azkia; Kasasiah, Ahsanal; Rahmasari, Ratika; Raekiansyah, Muhareva; Rohmah, Siti; Meilani, Nanda Diva; Septi, Annisa Frastica; Zahro, Aurora Fatimatuz; Annajla, Fathina; Hermosaningtyas, Anastasia Aliesa; Hilmi, Indah Laily
Jurnal Bioteknologi & Biosains Indonesia (JBBI) Vol. 10 No. 2 (2023)
Publisher : BRIN - Badan Riset dan Inovasi Nasional

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55981/jbbi.2023.2557

Reliable clinical diagnosis of Single Nucleotide Polymorphisms (SNPs) is necessary for personalizing tamoxifen medication according to CYP2D6*10 genetic variations. Our research aimed to create a recombinant plasmid for external control material with a molecular size of 3812 bp. The recombinant plasmid was achieved by cloning an 838 bp gene insert of CYP2D6*10 rs1065852 into a 2974 bp pJET1.2 plasmid into Escherichia coli DH10B and selection on ampicillin agar medium. Isolated E. coli recombinants provided the plasmid molecules for analysis. Bi-directional sequencing and Real-Time PCR confirmed the presence of wild-type and mutant rs1065852 DNA fragments in the plasmid, namely homozygote CC and TT. The conclusion is that we have successfully introduced a novel recombinant plasmid developed by cloning the SNP rs1065852, which carries the 100C>T mutation, using pJET 1.2/blunt system, which could significantly enhance the accuracy of clinical SNP diagnostics for personalized medicine in breast cancer treatment.

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