Serum microRNAs as new biomarkers for detecting subclinical hemolysis in the nonacute phase of G6PD deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies worldwide. Patients with G6PD deficiency are usually asymptomatic throughout their life but can develop acute hemolysis after exposure to free radicals or certain medications. Several studies have shown that serum miRNAs can be used as prognostic biomarkers in various types of hemolytic anemias. However, the impact of G6PD deficiency on circulating miRNA profiles is largely unknown. The present study aimed to assess the use of serum miRNAs as biomarkers for detecting hemolysis in the nonacute phase of G6PD deficiency. Patients with severe or moderate G6PD Viangchan (871G > A) deficiency and normal G6PD patients were enrolled in the present study. The biochemical hemolysis indices were normal in the three groups, while the levels of serum miR-451a, miR-16, and miR-155 were significantly increased in patients with severe G6PD deficiency. In addition, 3D analysis of a set of three miRNAs (miR-451a, miR-16, and miR-155) was able to differentiate G6PD-deficient individuals from healthy individuals, suggesting that these three miRNAs may serve as potential biomarkers for patients in the nonhemolytic phase of G6PD deficiency. In conclusion, miRNAs can be utilized as additional biomarkers to detect hemolysis in the nonacute phase of G6PD deficiency.

Glucose-6-phosphate dehydrogenase is dispensable for human erythroid cell differentiation in vitro.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs cellular processes under oxidative stress. Individuals with severe G6PD deficiency still produce sufficient numbers of erythrocytes. Nevertheless, the G6PD independence of erythropoiesis remains questionable. This study elucidates the effects of G6PD deficiency on the generation of human erythrocytes. Peripheral blood-derived CD34-positive hematopoietic stem and progenitor cells (HSPCs) of human subjects with normal, moderate, and severe G6PD activities were cultured in two distinct phases: erythroid commitment and terminal differentiation. Regardless of G6PD deficiency, HSPCs were able to proliferate and differentiate into mature erythrocytes. There was no impairment in erythroid enucleation among the subjects with G6PD deficiency. To our knowledge, this study is the first report of effective erythropoiesis independent of G6PD deficiency. The evidence firmly indicates that the population with the G6PD variant could produce erythrocytes to an extent similar to that in healthy individuals.

Impairment of Invasion and Maturation and Decreased Selectivity of Plasmodium falciparum in G6PD Viangchan and Mahidol Variants.

BACKGROUND: Protection against Plasmodium falciparum is observed in a population deficient in glucose-6-phosphate dehydrogenase (G6PD), particularly in African and Mediterranean regions. However, such protection remains unknown among G6PD-deficient individuals in Southeast Asia. METHODS: In this study, we assessed the invasion and maturation of P falciparum K1 in a culture of erythrocytes isolated from Thai subjects carrying Viangchan (871G > A) and Mahidol (487G > A). RESULTS: We found that the parasites lost their ability to invade hemizygous and homozygous G6PD-deficient erythrocytes of Viangchan and Mahidol variants in the second and third cycles of intraerythrocytic development. It is interesting to note that P falciparum parasites selectively grew in erythrocytes from hemi- and homozygous genotypes with normal G6PD activity. Moreover, externalization of phosphatidylserine upon P falciparum infection was significantly increased only in Viangchan hemizygous variant cells. CONCLUSIONS: This study is the first to show that blockage of invasion in long-term culture and potentially enhanced removal of parasitized erythrocytes were observed for the first time in erythrocytes from Viangchan and Mahidol G6PD-deficient individuals.