In:
Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-4-9)
Abstract:
Primaquine (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 10 ( p -value) = 2.44] and two less-known SNPs, rs2230037 [−log 10 ( p -value] = 2.60), and rs28470352 [−log 10 ( p -value) = 2.15]; A376G and rs2230037 were in very strong linkage disequilibrium with each other ( R 2 = 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.
Type of Medium:
Online Resource
ISSN:
1664-8021
DOI:
10.3389/fgene.2021.645688
DOI:
10.3389/fgene.2021.645688.s001
DOI:
10.3389/fgene.2021.645688.s002
DOI:
10.3389/fgene.2021.645688.s003
DOI:
10.3389/fgene.2021.645688.s004
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606823-0
