Molecular Characterisation of Glucose-6-Phosphate Dehydrogenase Deficiency Variants in Malaria-Endemic Communities in Anambra State

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in Nigeria and poses a clinically significant risk of haemolytic anaemia triggered by oxidative stress from antimalarial drugs and infectious illness. This study molecularly characterises G6PD deficiency variants in malaria-endemic communities in Anambra State, determining variant prevalence and their association with haemolytic susceptibility. Three hundred and twenty individuals from four communities in Anambra East and Oyi LGAs were enrolled. G6PD enzyme activity was determined by the fluorescence spot test and quantitative spectrophotometric method. DNA was extracted from EDTA blood samples and the G6PD gene exons 4, 5, 6, 8, 10, and 11 were amplified by polymerase chain reaction and sequenced using Sanger sequencing. Haemolytic parameters including haemoglobin, indirect bilirubin, lactate dehydrogenase, and haptoglobin were measured to characterise haemolytic risk. G6PD deficiency was detected in 19.4 percent of the study population. Molecular characterisation identified G6PD A- (c.202G>A/c.376A>G) as the predominant variant, accounting for 74 percent of deficient subjects. G6PD Betica (c.968T>C) was identified in 11 percent and a novel variant not previously reported in the Nigerian literature was identified in three individuals. Haemolytic marker profiles confirmed that G6PD A- homozygotes had the most severe haemolytic susceptibility. Coexistence of G6PD deficiency and sickle cell trait was detected in 4.7 percent of subjects. This characterisation data provides a basis for genotype-guided antimalarial treatment and targeted newborn G6PD screening in Anambra State. Keywords: G6PD deficiency, molecular characterisation, haemolytic anaemia, Anambra State, G6PD variants.