Genetic variants of human erythrocyte glucose 6‐phosphate dehydrogenase: new variants in West Africa characterized by column chromatography

Abstract

Five electrophoretically slow-moving genetic variants of glucose 6-phosphate dehydrogenase are described: four are from Nigeria and one is from Togo. All variants have normal or moderately reduced activity, and they are not associated with adverse clinical or haematological manifestations. Three variants have been fully characterized and are different from all previously described ones. Two variants have been partially characterized and at least one of them is also probably new. The overall population incidence of sporadic variants of G6PD in the Nigerian population is 0-3%. In the course of this study a previously described ion-exchange chromatographic technique for the characterization of G6PD variants has been extensively evaluated. Data are given on ten different variants to demonstrate the high resolving power of this technique.

Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia.

“…G6PD Mediterranean is one of the best-studied G6PD variants (23); it is polymorphic and is associated with acute hemolytic anemia, including favism. G6PD Ilesha is a sporadic variant from West Africa, found in a patient with sickle cell anemia (24). G6PD Metaponto is asymptomatic; since it was encountered in two unrelated people in Lucania (Southern Italy), it may be polymorphic in that region.…”

Genetic heterogeneity of "normal" human erythrocyte glucose-6-phosphate dehydrogenase: an isoelectrophoretic polymorphism.

“…In order to verify the suggestion that both G6PD B and G6PD A were heterogeneous, we have analyzed in some detail their kinetic properties and their chromatographic behavior. The latter technique has been shown to have a high resolving power even for variants that are otherwise undistinguishable (16).…”

Characterization of Glucose-6-Phosphate Dehydrogenase Variants in the Sudan – Including Gd^Khartoum, a Hyperactive Slow Variant

“…The other slow non-deficient var iants like Minas Gerais, M adrona, Ibadan-A ustin and Ita-Bale, all detected in Brazil, could be differentiated from G d Khartoum j-,y their much slower mobility (65-82%) in TEB buffer and biochemical characteristics. Further, two other non-de ficient variants, (G dAyuuhaya in Thailand and G d Pmar Del Rl° in Cuba) have lower en zyme activity and m igration rate as well as low Km o f G6P [4], The 4 variants with slower electrophoretic mobility in TEB (72-96%) and normal enzyme activity, de tected in West Africa, cannot be accu rately differentiated from G d Khar,oum due to limited biochemical characterization [11], However, the Km for G6P of all these 4 variants was much lower than the pres ent G d Kharloum (40-81 pM) while they had higher Km for N A D P (7.7-20.6 pM). It should be pointed out that a great deal of inter laboratory variations o f enzyme ki netics remains a problem for confirm ation of the G6PD variants in general.…”

“…Electrophoretic and biochemical S aha/Sam uel with normal activity and of slower m igra tion in the tris-ED TA-borate (TEB) buffer system have been described in Greece, Africa (Bantu) and Brazil (Tacoma) [14]. In addition, 4 slow variants with normal activity have been reported in West Africa by Usanga et al [11], but they were not bi ochemically characterized. Several exam ples of hyperactive G 6PD (400% active) variants called G d Hcktocn have also been described in US Whites [15].…”