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Identifikasi Kandidat Target Obat Ulcerative Colitis (UC) Menggunakan Pendekatan Bioinformatika Menuju Precision Medicine Sianu, Rahman Sumani; Jannah, Miftahul; Mauri, Ariesa; Ayu L, Putri; Yuni N, Eka; Pratiwi G, Annisa
Herbal Medicine Journal Vol 8 No 2 (2025): Herbal Medicine Journal
Publisher : Program Studi S1 Farmasi, STIKES Senior, Medan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58996/hmj.v8i2.169

Abstract

Ulcerative Colitis (UC) is a chronic inflammation of the lining of the digestive tract, primarily in the rectum and colon. Genetics is a factor in the occurrence of UC. This becomes a challenge in finding new drugs to treat the disease based on certain genes. So, the aim of this research is to identify candidate therapeutic targets in UC. We used the Genomic-Wide Association Studies (GWAS) catalog to collect data on gene variations associated with UC and then identified missense genes as target genes in this study using HaploReg v4.2. The final stage, to determine the pharmacological action of drugs on the target genes, we used Drugbank and the Drug-Gene Interaction database (DGIdb). Our analysis yielded 760 SNPs associated with UC disease. In the next stage, score classification was performed based on six functional annotations including Missense, cis-eQTL, Biological Process, Cellular Component, Molecular Function, and KEGG Molecular Pathway. Based on these annotation criteria, 16 genes with a score ≥2 were identified, namely PRKCQ, TLR4, IFIH1, CARD9, TYK2, CD6, NOD2, PLCG2, SMAD3, FCGR2A, IL-23R, SH2B3, IL-17REL, FUT2, GSDMB, and IL-7R. These genes became biomarkers and drug targets in this study. From the 16 genes, 83 drugs were obtained using the Drugbank and DGIdb databases. However, there are 4 drugs that can be proposed as candidates for the treatment of UC disease, namely tamoxifen (PRKCQ Inhibitor), cyclobenzaprine (TLR4 Inhibitor), benzoyl peroxide (PRKCQ Inhibitor), and pazopanib (SH2B3 Inhibitor). These drugs are candidates for UC therapy because they have not yet been tested either preclinically or clinically for the indication of ulcerative colitis. This genomic analysis significantly aids in identifying genes closely associated with UC and provides insights for defining important targets in new drug discovery. Therefore, further exploration and research related to these drugs are crucial, offering a promising path to advance UC treatment strategies.
Dampak Variasi Genetik terhadap Respon Terapi dan Potensi Hemolisis Anemia dari Penggunaan Primakuin melalui Pendekatan Farmakogenetika Sianu, Rahman Sumani; Ghifari, Annisa Abdi; Ma’ruf, Muhammad; Nur Jannah, Eka Yuni; Lestari, Putri Ayu
Herbal Medicine Journal Vol 9 No 1 (2026): Herbal Medicine Journal
Publisher : Program Studi S1 Farmasi, STIKES Senior, Medan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58996/hmj.v9i1.219

Abstract

Primaquine is essential for radical cure of Plasmodium vivax malaria but poses hemolysis risk in G6PD-deficient individuals and shows variable therapeutic responses. Genetic polymorphisms in drug-metabolizing enzymes and transporters contribute to these inter-individual variations. To investigate genetic variants in G6PD, SLCO2B1, and MAOA genes that influence primaquine safety and efficacy, and to assess their clinical implications for personalized antimalarial therapy. Method the database used in this study is PhramGKB. Genetic polymorphisms in four candidate genes were analyzed for associations with hemolysis, anemia, therapeutic efficacy, and malaria recurrence. Statistical analyses determined the strength and significance of genotype-phenotype associations. Result G6PD variants rs1050828 and rs1050829 showed strong associations with hemolysis (p<0.01) and anemia (p=0.001). SLCO2B1 variant rs12422149 was associated with reduced chloroquine-primaquine efficacy (p=0.01). MAOA variant rs6323 increased malaria recurrence risk (p=0.03). Conclusion multiple genetic variants significantly impact primaquine safety and efficacy. These findings support pharmacogenetic-guided personalized antimalarial therapy to optimize outcomes and minimize adverse events, contributing to malaria elimination efforts.