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G6PD polymorphisms and hemolysis after antimalarial treatment with low single-dose primaquine: a pooled analysis of six African clinical trials
journal contribution
posted on 2023-06-10, 00:01 authored by Nuno Sepúlveda, Lynn Grignard, Jonathan Curry, Laleta Mahey, Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Sam A Coulibaly, Bronner BP Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, Chi EziefulaChi Eziefula, othersPrimaquine (PQ) is an antimalarial drug with the potential to reduce malaria transmission due to its capacity to clear mature Plasmodium falciparum gametocytes in the human host. However, the large-scale roll-out of PQ has to be counterbalanced by the additional risk of drug-induced hemolysis in individuals suffering from Glucose-6-phospate dehydrogenase (G6PD) deficiency, a genetic condition determined by polymorphisms on the X-linked G6PD gene. Most studies on G6PD deficiency and PQ-associated hemolysis focused on the G6PD A- variant, a combination of the two single nucleotide changes G202A (rs1050828) and A376G (rs1050829), although other polymorphisms may play a role. In this study, we tested the association of 20 G6PD single nucleotide polymorphisms (SNPs) with hemolysis measured seven days after low single dose of PQ given at the dose of 0.1 mg/kg to 0.75 mg/kg in 957 individuals from 6 previously published clinical trials investigating the safety and efficacy of this drug spanning five African countries. After adjusting for inter-study effects, age, gender, baseline hemoglobin level, PQ dose, and parasitemia at screening, our analysis showed putative association signals from the common G6PD mutation, A376G [-log (p-value) = 2.44] and two less-known SNPs, rs2230037 [-log (p-value] = 2.60), and rs28470352 [-log (p-value) = 2.15]; A376G and rs2230037 were in very strong linkage disequilibrium with each other (R = 0.978). However, when the effects of these SNPs were included in the same regression model, the subsequent associations were in the borderline of statistical significance. In conclusion, whilst a role for the A- variant is well established, we did not observe an important additional role for other G6PD polymorphisms in determining post-treatment hemolysis in individuals treated with low single-dose PQ. 10 10 10 2
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Publication status
- Published
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- Published version
Journal
Frontiers in GeneticsISSN
1664-8021Publisher
Frontiers MediaExternal DOI
Volume
12Page range
1-12Article number
a645688Event location
SwitzerlandDepartment affiliated with
- Global Health and Infection Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-06-03First Open Access (FOA) Date
2021-06-03First Compliant Deposit (FCD) Date
2021-06-03Usage metrics
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