A Review of Clinical Pharmacogenetics Studies in African Populations

Abstract

Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.

The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations

“…The African continent is the cradle of human origin and African populations are characterized by high genetic diversity and complex population structure. Despite this genetic variation, drug efficacy and safety have not been comprehensively studied in the populations of sub-Saharan Africa (SSA) (Radouani et al, 2020). This is of specific relevance to SSA, where high burdens of disease are amplified by non-optimal treatment outcomes.…”

Emerging Role for Pharmacogenomics in HIV Research in Africa

“…A number of African studies, were premised on observations from the USA and Europe, that showed association between warfarin drug response and variation in two genes, CYP2C9 and VKORC1. Associations between warfarin levels and VKORC1 and CYP2C9 genetic variants were corroborated in Egyptians, Ghanaians and South Africans, but not in Sudanese and Kenyan individuals [12]. Such results speak to the heterogeneity of Africans among themselves and with other populations.…”

The Evolving Antibiotic Profile of Paediatric Urinary Tract Infections at a Tertiary Hospital in Cape Town

“…CYP3A4 and ABCB1 have been associated with response to cyclosporine therapy for renal transplant recipients; CYP3A4 and CYP3A5 haplotypes are associated with tacrolimus clearance, an immunosuppressive therapy sometimes used to treat SR-FSGS; and variants in CYP3A4 and ADRB2 have been associated with the blood pressure-lowering drugs amlodipine and ramipril, respectively. (83) The implementation of personalized pharmacogenetics in SSA requires additional genetic and clinical research, including clinical trials to identify population-specific variants that affect drug metabolism, clearance and clinical efficacy. An example is renal risk reduction (R3)-randomized clinical trial in Nigeria that is designed to study the efficacy of blocking the renin-angiotensin-aldosterone system with inexpensive ACEis to retard progression of kidney disease in patients with treated HIV infection and to determine if APOL1 HR status is associated with worse kidney outcomes among study participants.…”