South African Psychiatry - February 2019

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26 * SOUTH AFRICAN PSYCHIATRY ISSUE 18 2019
FEATURE PHARMACOGENOMIC T E S T I N G IN SOUTH AFRICAN PSYCHIATRY Aron B. Abera a * and Pierre M. Durand b a Inqaba Biotechnical Industries, Hatfield, Pretoria, South Africa b Evolutionary Studies Institute, University of the Witwatersrand, Johannesburg, South Africa *Corresponding author: aron.abera@inqababiotec.co.za An area of increasing interest in psychiatry is the use (and sometimes abuse) of pharmacogenomic analyses. Globally, pharmacogenomics already play a role in psychiatry treatment guidelines in the so-called ‘developed’ countries. This area of interest is poised to grow in South Africa, but there are important considerations for the local context that are largely unexplored. Perhaps the most pressing question is how appropriate the available pharmacogenomic analyses are for psychiatrists working in SA. To attempt to answer this all-encompassing question, a brief review of the aims, scope and methodologies in pharmacogenomics is warranted. PHARMACOGENOMICS: AIMS AND SCOPE An individual’s genetic make-up (the genotype) affects how their body responds to, and metabolises drugs (the phenotype). The term pharmacogenomics is a portmanteau of pharmacology and genomics and aims to match the individual’s genotype with the expected response to the prescribed drug. The majority of assays include both pharmacokinetic (PK) and pharmacodynamic (PD) genomic panels. Pharmacokinetic genes affect the body’s absorption, distribution, metabolism, and elimination of medications. The cytochrome P450 (CYP) enzyme family is the major PK mechanism and the genetic information used to assess variations in drug metabolism is most often based on this gene family. Approximately 90% of all drugs are metabolized by just seven different cytochrome enzymes including CYP1A2, CYP3A4, CYP3A5, CYPC19, CYP2D6, CYP2C9 and CYP2B69. CYP2D6, for example, contributes to the metabolism of 25% of most commonly prescribed medications including psychiatric medications like tricyclic antidepressants, opioids and anti-psychotics. Aron Berhanie Abera CYP2D6 IS A HIGHLY POLYMORPHIC GENE WITH OVER 130 SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) AND INCLUDES INSERTIONS, DELETIONS, DUPLICATIONS AND FRAME SHIFT MUTATIONS. THESE GENETIC VARIATIONS LEAD TO DECREASED, INCREASED OR NON-FUNCTIONAL ENZYMATIC ACTIVITY IN THE INDIVIDUAL. Allelic variants are sometimes very broadly classified as poor metabolizers (PM), extensive metabolizers (EM), intermediate metabolizers (IM) and ultra-rapid metabolizers (UM) according to the pharmacokinetics. SOUTH AFRICAN PSYCHIATRY ISSUE 18 2019 * 27
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