G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19

Abstract

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10^-3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.

Fig. 1. G6PD missense variant distribution across African populations.

A G6PD allele frequencies in populations from high coverage African ADME Dataset (HAAD) countries. Confidence intervals for allele frequencies based on the equal or given proportions test the 95% significance level. Dark shading indicates country populations assessed, light shading indicates countries containing HAAD individuals but were not evaluated as individual countries due to fewer than 25 representative individuals. B Allele frequencies of missense variants in HAAD, and African superpopulation groups from gnomAD and the KGP. C Structural representation of the G6PD homodimer with missense residues highlighted in blue colour on both chains with bound NADP (NADP shown in red–turquoise–blue).