Pharmacogenomic diversity in psychiatry: Challenges and Opportunities in Africa

Abstract

AbstractBackgroundStudies on the pharmacogenomic of psychiatric drugs have slowly identified genetic variations that influence drug metabolism and treatment outcomes, including response, remission, and side effects. However, most of these studies predominantly entered on populations of European descent. As a result, there remains a significant knowledge gap pertaining to the extent of pharmacogenomic diversity among African populations and this raises a major question about the validity of translating the current evidence to enable pharmacogenomic genetic testing (PGx) for this population. The objective of this review was to appraise previous pharmacogenomic studies conducted in the African population, with a focus on psychiatric medications.MethodsA systematic search was conducted on PubMed, Scopus, and Web of Science to identify studies published in the English language from inception up to February 06, 2023. The primary outcomes were treatment response, remission, side effects, and drug metabolism in African patients with major psychiatric disorders, such as depression and schizophrenia. Conference papers, abstracts, or articles lacking full text were excluded. To ensure data accuracy, two reviewers independently performed data extraction using the PRISMA reporting guideline.ResultsThe review included 42 pharmacogenetics and pharmacogenomics studies that explored the genetic profiles of African psychiatric patients who received pharmacological therapy. While we found a limited number of studies, they provided strong evidence of pharmacogenomic diversity in African populations, highlighting the importance of investigating the role of genetics in the treatment of psychiatric disorders in this population. The frequencies of cytochrome P450 (CYP450) gene genotypes show high variability. For instance, up to 28% of individuals of North Africans and Ethiopians are ultrarapid metabolizers to several medications, attributed to increased activity of theCYP2D6enzymes, in contrast to 10% prevalence among Caucasians and 1% within Hispanic, Chinese, and Japanese populations. Genotyping theCYP1A2gene and using therapeutic drug monitoring (TDM) improved the effectiveness and safety of Clozapine in Tunisian patients with schizophrenia. In Ethiopia, 5.2% of the subjects were found to be poor metabolizers of S-mephenytoin, with a frequency of theCYP2C19*2allele at 14% and theCYP2C19*3allele at 2%.Among South African patients with schizophrenia, two gene variants (rs13025959 in theMYO7Bgene with the ‘C’ allele and rs10380 in theMTRRgene with the ‘T’ allele) were found to impact treatment response to ???.ConclusionThe review has identified evidence of pharmacogenomic diversity in African populations and recommended expanding pharmacogenomic studies while introducing PGx in this population. For the few characterized genes, Africans exhibit qualitative and quantitative differences in the profile of pharmacogenetic variants when compared to other ethnic groups. Limited research funding, inadequate infrastructure, and a shortage of skilled human resources might be a challenge, but by building upon local successes and through collaborations with international partners, it is possible to leverage global genetic knowledge and sequencing technology for the development of personalized treatment approaches in Africa.