Journal
PHARMACOGENOMICS JOURNAL
Volume 21, Issue 6, Pages 649-656Publisher
SPRINGERNATURE
DOI: 10.1038/s41397-021-00242-8
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Funding
- GSK
- NIH/NHGRI as part of the H3Africa Consortium [U54HG006938]
- NIH Common Fund Award/NHGRI [U24HG006941]
- Department of Science and Technology
- Wellcome Trust [099310/Z/12/Z]
- NIH/NHGRI [1U54AI110398]
- National Human Genome Research Institute, National Institutes of Health (NIH/NHGRI) [U54HG003273]
- Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council
- South African Research Chairs Initiative of the Department of Science and Technology
- National Research Foundation of South Africa [84177]
- South African National Research Foundation [SFH170626244782]
- Bill & Melinda Gates Foundation
- Wellcome Trust [099310/Z/12/Z] Funding Source: Wellcome Trust
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Variants in the G6PD gene among individuals from sub-Saharan Africa show significant diversity, potentially impacting the efficacy of chloroquine/hydroxychloroquine in COVID-19 treatment. Allele frequency differences in G6PD deficiency-related variants exist among different African sub-populations, which may affect drug efficacy and side effects.
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 x 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.
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