Aspek Farmakogenomik Pada Polimorfisme Gen C957T Pasien Skizofrenia Dengan Terapi Aripiprazole
Abstract
Polimorfisme gen C957T merupakan synonymous mutation yang terletak pada pasang basa ke-957 gen DRD2. Aripiprazole merupakan antipsikotik generasi kedua yang mempunyai sifat agonis parsial, memiliki selektivitas fungsional terhadap berbagai isoform DRD2, dan memiliki efektivitas yang baik terhadap skizofrenia dengan efek samping yang minimal. Tujuan penulisan ini adalah untuk memberikan telaah pustaka mengenai polimorfisme gen C957T beserta tatalaksana aripiprazole yang berkaitan dengan kejadian skizofrenia yang dilihat dari sudut pandang farmakogenomik. Jenis telaah yang digunakan dalam artikel ini berbentuk literature review terhadap 30 literatur dari berbagai jurnal maupun textbook. Skizofrenia dikaitkan dengan hipotesis dopamin, yaitu konsep dari second neurotransmitter-based. Formulasi paling sederhana dari hipotesis ini adalah gejala positif skizofrenia merupakan hasil dari aktivitas dopaminergik yang melibatkan traktus mesokortikal dan mesolimbik, dimana terjadi pelepasan dopamin yang berlebihan. Efektivitas antipsikotik terutama aripiprazole, termasuk efek sampingnya, dipengaruhi oleh single nucleotide polymorphism (SNP) pada reseptor tersebut. Dari telaah terhadap berbagai studi didapatkan bahwa aripiprazole merupakan antipsikotik yang memblok DRD2 postsinap dengan kuat, memiliki afinitas yang sangat tinggi terhadap DRD2, serta memiliki sifat agonis parsial yang berperan dalam profil terapeutik aripiprazole yang baik pada pasien skizofenia dengan polimorfisme C957T.
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DOI: https://doi.org/10.24853/jkk.18.1.94-103
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