Views from the London School of Hygiene & Tropical Medicine

New research shows how Glucose-6-phosphate dehydrogenase enzyme mutations protect against malaria

Plasmodium falciparum - credit Samana Schwank, LSHTMA new study in Tanzania led by researchers at the London School of Hygiene & Tropical Medicine has provided insights into how gene mutations associated with deficiency in a vital blood enzyme, glucose-6-phosphate dehydrogenase, can protect against malaria.

Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme that protects human red blood cells from oxidative damage. Many genetic variants of the G6PD gene are found among African populations. Like the well-known sickle cell trait, these mutations can lead to serious disorders such as haemolytic anaemia, but are also associated with protection against severe malaria.

However, epidemiological studies over several decades have failed to provide a clear picture as to how G6PD-deficiency protects against malaria. Whether females, carrying either one or two copies of mutant genes, males carrying one copy, or both genders are protected is uncertain, due in part to the complexity of the G6PD locus.

In this study, published recently in PLoS Genetics, more than 30 G6PD genetic markers in 506 Tanzanian children with severe malaria and 477 children without malaria were analysed.  The researchers found that only females with one normal and one mutant copy of the gene (heterozygotes) were protected from severe malaria. The G6PD gene, residing in the human X chromosome, was found to be under evolutionary pressure with the likely mechanism being selection by malaria.

This work provides insight into an important mechanism of malaria protection, but also as the treatment of malaria can cause severe hemolysis in G6PD-deficient patients, it could assist with screening patients for deficiency before treatment.

Manjurano A, Sepulveda N, Nadjm B et al. African Glucose-6-Phosphate Dehydrogenase Alleles Associated with Protection from Severe Malaria in Heterozygous Females in Tanzania. PLoS Genet. 2015 Feb 11;11(2):e1004960. doi: 10.1371/journal.pgen.1004960. eCollection 2015 Feb.

Image: Plasmodium falciparum courtesy of Samana Schwank, LSHTM

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