Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border.

Germana Bancone,Nicholas J White,Daniel M Parker,Nongnud Chowwiwat,Cindy S Chu,Raweewan Somsakchaicharoen,François H Nosten,Prakaykaew Charunwatthana,Laurent Rénia

doi:10.1371/journal.pone.0116063

Abstract

Mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST), G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A) genotype. The remaining subjects had Chinese-4 (392G>T), Viangchan (871G>A), Açores (595A>G), Seattle (844G>C) and Mediterranean (563C>T) variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.

Highlights

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic disorder in humans
G6PD deficiency is common in this malaria endemic region along the northwestern border of Thailand
The present study shows that in the population living along the Thailand-Myanmar border, G6PD Mahidol enzymatic activity in hemizygous males is below 10% of the activity detected in G6PD normal males of the same population

Summary

Introduction

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic disorder in humans. It is prevalent throughout Africa, Asia, Southeast Asia and parts of South America, where malaria is endemic [1]. Different mutations in the gene encoding for G6PD cause varying degrees of protein instability that renders the mature red blood cells more susceptible to oxidative damage. Antimalarial drugs such as the 8-aminoquinolines (primaquine, tafenoquine) cause dose-dependent damage to G6PD deficient red blood cells resulting in intravascular haemolysis and removal of damaged erythrocytes by the spleen. As with other sex-linked disorders, phenotypic screening of male subjects is the preferred approach to assess G6PD deficiency prevalence and allelic frequency in the population

Methods

Results

Conclusion