Pharmacogenomic Research in South Africa: Lessons Learned and Future Opportunities in the Rainbow Nation

Abstract

South Africa, like many other developing countries, stands to benefit from novel diagnostics and drugs developed by pharmacogenomics guidance due to high prevalence of disease burden in the region. This includes both communicable (e.g., HIV/AIDS and tuberculosis) and non-communicable (e.g., diabetes and cardiovascular) diseases. For example, although only 0.7% of the world’s population lives in South Africa, the country carries 17% of the global HIV/AIDS burden and 5% of the global tuberculosis burden. Nobel Peace Prize Laureate Archbishop Emeritus Desmond Tutu has coined the term Rainbow Nation, referring to a land of wealth in its many diverse peoples and cultures. It is now timely and necessary to reflect on how best to approach new genomics biotechnologies in a manner that carefully considers the public health needs and extant disease burden in the region. The aim of this paper is to document and review the advances in pharmacogenomics in South Africa and importantly, to evaluate the direction that future research should take. Previous research has shown that the populations in South Africa exhibit unique allele frequencies and novel genetic variation in pharmacogenetically relevant genes, often differing from other African and global populations. The high level of genetic diversity, low linkage disequilibrium and the presence of rare variants in these populations question the feasibility of the use of current commercially available genotyping platforms, and may partially account for genotype-phenotype discordance observed in past studies. However, the employment of high throughput technologies for genomic research, within the context of large clinical trials, combined with interdisciplinary studies and appropriate regulatory guidelines, should aid in acceleration of pharmacogenomic discoveries in high priority therapeutic areas in South Africa. Finally, we suggest that projects such as the H3Africa Initiative, the SAHGP and PGENI should play an integral role in the coordination of genomic research in South Africa, but also other African countries, by providing infrastructure and capital to local researchers, as well as providing aid in addressing the computational and statistical bottlenecks encountered at present.

Genomic Research Data Generation, Analysis and Sharing – Challenges in the African Setting

“…Significant disparities currently exist among SSA countries in genomics research capacity (Adedokun et al 2016). South Africa has the highest genomics research output, which is reflected in the investments made in its genomics and biotechnology sector (Hardy et al 2008;Warnich et al 2011;Ndimba and Thomas 2008;Motari et al 2004). The study findings call for African governments to increase their investments in building local capacity, provide a sustainable research environment, and encourage joint genomics research among those affiliated with SSA universities.…”

Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African populations: focus on efavirenz and nevirapine

“…The most important class of the drug metabolizing enzymes is the cytochrome P450 (CYP450) family, which is involved in phase I metabolism of various endogenous and exogenous compounds, including the majority of clinically prescribed drugs (Warnich et al, 2011). CYP450 enzymes are heme oxygenases, found mainly in the liver.…”

Editorial (Public Health Pharmacogenomics and the Design Principles for Global Public Goods – Moving Genomics to Responsible Innovation)

“…For example, a scoping analysis of 344 studies in health and allied sciences addressing patients', clinicians' and researchers' priorities for research, found that only nine considered the extent to which questions posed by researchers matched questions of relevance to patients and clinicians [12]. Furthermore, translation of pharmacogenomics into the clinic remains a challenge, especially in low and middle income countries that can benefit much from effective and safe therapeutic regimes [13].…”

“…These principles were outlined by Elinor Ostrom, Nobel Laureate in Economic Sciences in 2009 ( Table 1, with modifications by Pang) [14,15]. CPPM readers are encouraged to read the seminal works on the governance of the commons and institutional diversity by Ostrom [15,16], and the ways in which these can impact behavior in society, including our 21 st century knowledge society [8] that is being shaped by globalization of genomics and personalized medicine [5,11,13].…”