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.

Molecular dynamics of G6PD variants from sub-Saharan Africa

“…In previous work, we observed large differences in allele frequency for G6PD variants in African populations [13] . There were nine G6PD coding variants which induce missense type substitutions of amino acids identified across a large sample of African population data.…”

“…1 ). Variants of interest detected in African population datasets [13] , are highlighted in Fig. 1 .…”

“…Variation in the G6PD gene has been linked to adverse drug reactions, but most studies to date have investigated variants common in Asian [23] and Mediterranean populations [24] . Previous work showed there are numerous variants which are diverse in sub-Saharan African populations [13] . This study has investigated the impact of African population variation on the structure of G6PD enzyme through molecular dynamics simulation.…”

SWAAT Bioinformatics Workflow for Protein Structure-Based Annotation of ADME Gene Variants

“…For instance, depending on the genetic variability, the well-studied CYP2D6 ADME gene is associated with ultrarapid, intermediate, or poor metabolization of tamoxifen [2]. The polymorphism of ADME genes is a distinctive property of different populations [3][4][5][6]. For example, the rs1050828 T variant is known to cause an acute deficiency in G6PD.…”

“…For example, the rs1050828 T variant is known to cause an acute deficiency in G6PD. Its occurrence among genetically diverse groups (reflected in self-identify) in South Africa has been shown to vary significantly even among geographically neighboring populations [3]. Moreover, clinically actionable variants of ADME genes deviate significantly between Sub-Saharan Africa and other worldwide populations [7].…”