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.
Highlights
The glucose-6-phosphate dehydrogenase (G6PD) enzyme is responsible for the production of nicotinamide adenine dinucleotide phosphate (NADPH) which is required in the glutathione mediated detoxification of reactive oxygen species [7]
We suggest that variations in the G6PD gene could significantly affect risk of adverse effects of CQ/HCQ, and recommend that this should be evaluated in clinical trials of CQ/HCQ treatment for COVID-19
We report the prevalence of a key G6PD variant, rs1050828, in 11,030 Africans from four countries in west, east and southern Africa, and show that is the variant allele common in Africa overall, but that there are very large differences between different groups, even between those who reside in close proximity
Summary
Aminoquinolines are suspected to exert their antimalarial effect by increasing oxidative stress via production of haembased reactive oxygen species [6]. The G6PD enzyme is responsible for the production of nicotinamide adenine dinucleotide phosphate (NADPH) which is required in the glutathione mediated detoxification of reactive oxygen species [7]. In the case of inactive/deficient G6PD, the NADPH supply may not be sufficient to neutralise the reactive oxygen species induced by CQ/HCQ and other drugs with similar mechanisms of action. It mostly occurs in males who are hemizygous for deleterious variants of the G6PD gene and in females with homozygous deleterious variants. Symptoms have been observed in females with heterozygous combinations due to X-inactivation effects [9]
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