Some Mexican glucose-6-phosphate dehydrogenase variants revisited

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency appears to be fairly common in Mexico. We have now examined the DNA of three previously reported electrophoretically fast Mexican G6PD variants, -G6PD Distrito Federal, G6PD Tepic, and G6PD Castilla. All three of these variants, believed on the basis of biochemical characterization and population origin to be unique, have the G----A transition at nucleotide 202 and the A----G transition at nucleotide 376, mutations that we now recognize to be characteristic of G6PD A-. Two other Mexican males with G6PD deficiency were found to have the same mutation. All five have the (NlaIII/FokI/PvuII/PstI) haplotype characteristic of G6PD A -in Africa. Since the PvuII+ genotype seems to be rare in Europe, we conclude that all of these G6PD A - genes had their ancient origin in Africa, although in many of the Mexican patients with G6PD A -202A/376G the gene may have been imported more recently from Spain, where this variant, formerly known as G6PD Betica, is also prevalent.

Definition of the Mutations of G6PD Wayne, G6PD Viangchan, G6PD Jammu, and G6PD ‘Lejeune’

“…As has been noted in previous studies [1,12,13,18], considerable differences in biochemical characteris tics were reported in variants that have now proved to be identical. As shown in table 1, the major differ ences between G6PD Jammu and G6PD Viangchan were in the utilization of 2-deoxy glucose-6-phosphate.…”

“…Ex amination of the original data on G6PD Jammu also showed a pH optimum of 9.5, but since all points fell within the broad normal range the pH-activity curve had been designated as normal. Thus we sec that, as in an earlier study [12], biochemically dissimilar vari ants that prove to have the same mutation may seem much more similar when they are recharacterized.…”

“…Thus, in a recent review of 46 variants [8] we found that only 23 different mutations had been found. It is of interest that this was the case not only with polymorphic mu tations such as G6PD A- [9][10][11][12], G6PD Mediterrane an [2,9], and G6PD Canton [13,14], but also with spo radic variants that cause chronic hemolytic anemia and are therefore presumably subject to adverse se lection.…”

X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6-phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons

“…G6PD has been an extraordinarily important enzyme in biomedical research for two primary reasons. One reason is that deficiency of G6PD, formerly called favism or primaquine sensitivity, is probably the most common hereditary enzymatic abnormality in humans (De Flora, 1981;Beutler et al, 1991a). Indeed, it has been estimated (Beutler, 1991) that over 200 million people worldwide manifest some form of deficiency of this cytosolic enzyme, ranging from mild, nonsymptomatic reductions of activity in erythrocytes to severe deficiency associated with chronic hemolytic anemia and environmentally (food, drug) induced hemolytic crises (reviewed by Yoshida and Beutler, 1983;Beutler, 1990Beutler, , 1991.…”

DNA sequencing analysis of several G6PD variants previously defined by PCR-restriction enzyme analysis

“…To date a total of 18 different G6PD variants have been observed in Mexico (Arámbula et al 2000;Arámbula 2002;Beutler et al 1991b;Beutler et al 1992;Lisker et al 1981;Medina et al 1995;Medina et al 1997;Vaca et al 2002;Vaca et al 2003) and 3 of them (both G6PD A -variants along with G6PD Santamaria variant) account for more than 80% of the overall prevalence of G6PD deficiency in Mexico (Arámbula 2002;Lisker 1981;Vaca et al 2002).This pattern of common G6PD variants is similar to that seen in other parts of the Americas such as Costa Rica (Beutler et al 1991c), Cuba (Rovira et al 1994), and Brazil (Hamel 2002;Weimer 1998). …”