Glucose-6-phosphate dehydrogenase deficiency allelic variants and their prevalence in malaria patients in Eritrea

Abstract

Introduction: glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy with a relatively high frequency in malaria-endemic regions. In Eritrea, there is scanty knowledge of G6PD deficiency. The aim of the study was to characterize and determine the prevalence of four common G6PD allelic variants.

Methods: three hundred and fourteen dried blood spot samples from unrelated microscopically diagnosed malaria patient Eritrean ethnic groups living in five zobas (regions) of Eritrea were analysed by PCR-RFLP method to identify the G6PD B, G6PD A (A376G), G6PD A-(G202A), and G6PD Mediterranean (C563T) variants. To confirm the RFLP results, samples positive for A376G but negative for G202A variants were subjected to Sanger sequencing and a subset of PCR products (exon 5) directly sequenced to identify A376G and other mutations.

Results: for G6PD genotyping, G6PD B was detected in 87.5% and A376G detected in 12.5% of malaria patients, whereas G202A and C563T were absent. Bivariate statistical analysis showed a statistically significant association between G6PD genotypes and zoba (P < 0.004 < 0.05). Sequencing revealed the expected A376G variant. In exon 5, four common (A376G) mutations, three uncommon mutations rs782669677 (535G→A) and one potentially new mutation (451G→C), relative to the reference, mRNA NM_001042351 were detected. Bioinformatic analysis of these mutations' potential functional impact suggests minimal effect on protein function.

Conclusion: this is the first report indicating that G6PD B and G6PD A genotypes are prevalent in Eritrea. Similar findings were reported in neighboring countries. Further studies including phenotype analysis are needed to corroborate the observed results.