Glucose-6-phosphate Dehydrogenase Deficiency in Portugal: Biochemical and Mutational Profiles, Heterogeneity, and Haplotype Association

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. This deficiency in erythrocytes has a prevalence of 0.51 Ϯ 0.109 in the Caucasoid male population of Portugal. The frequency for deficiency-conferring genes is 0.39% in the Portuguese population. In the herein study populations males from areas of Portugal presenting with the highest prevalence of G6PD deficiency (Castelo Branco, Setúbal, Faro, and Lisbon) as well as similar subjects located in the border Center/North area of the country (Viseu) have been analyzed for biochemical parameters and screened for mutations and haplotypeassociated mutations commensurate with G6PD deficiency. Six intragenic restriction fragment length polymorphisms (RFLPs) were studied: exon 5, nt 376 A 3 G, FokI; intron 5, nt 611 C 3 G, PvuII; intron 8, nt 163 C 3 T, BspHI; exon 10, nt 116 G 3 A, PstI; exon 11, nt 1311 C 3 T, BclI; and intron 11, nt 93 T 3 C, NlaIII. New haplotypes were constructed with the inclusion of intron 11, nt 93 T 3 C, NlaIII, and only 5 of 64 possible haplotypes were found to show a marked linkage disequilibrium for several RFLPs and also for mutations and specific haplotypes. The control population (n ϭ 168 males) presented the G6PD B variant and corresponded to haplotypes I (Ϫ Ϫ ϩ ϩ Ϫ Ϫ), Ia (Ϫ Ϫ ϩ ϩ Ϫ ϩ), and VIIa (Ϫ Ϫ ϩ ϩ ϩ ϩ), in 91.8, 2.3, and 5.9%, respectively. The PCR and sequencing analysis of extracted DNAs from the deficient G6PD group showed 48.6% (16/33) of individuals with the G6PD AϪ mutation, corresponding to haplotype VIa (ϩ ϩ Ϫ ϩ Ϫ ϩ); 9% (3/33) with the Betica mutation and 18% (6/33) with the Santa Maria mutation, both of them associated with haplotype IVa (ϩ Ϫ Ϫ ϩ Ϫ ϩ); 6.1% (2/33) with the Mediterranean mutation associated with haplotype VIIa; 12.3% (4/33) with the Seattle mutation, 3.0% (1/33) with Gaohe mutation; and a new mutation, 3.0% (1/33), which we designated by G6PD Flores, all of them associated with haplotype I. © 2002 Elsevier Science (USA)

G6PD A- Deficiency and Severe Malaria in The Gambia: Heterozygote Advantage and Possible Homozygote Disadvantage

“…We performed Sequenom analyses for all sites (primers in Table 2). Additionally, for the T968C polymorphism, we amplified the surrounding region (forward primer: CATC TGTGGCCACAGTCATC; reverse primer: TGGTCATCA TCTTGGTGTAC, T annealing = 57 C), digested the amplified fragments using the MspI restriction enzyme (New England Biolabs, Ipswich, MA) as described in the work by Rodrigues and others, 16 and confirmed that it remains a valid genotyping approach in resource-limited settings. Amplification reactions were performed with Taq Platinum according to the manufacturer's protocols (Invitrogen/Thermo Fisher Scientific, Waltham, MA).…”

Novel point mutation in exon 12 of the glucose‐6‐ Phosphate Dehydrogenase Gene: G6PD Flores

“…There are a wide variety of G6PD deficiency associated mutations in the Portuguese population (7). In this study we report a new mutation in the G6PD gene that gives rise to a mild enzymatic deficiency in an individual from the island of Flores of the Azorean archipelago.…”

Glucose-6-Phosphate Dehydrogenase Deficiency in Children from 0 to 14 Years Hospitalized at the Pediatric Hospital David Bernardino, Luanda, Angola

“…Higher frequencies were detected among Palestinians in the Gaza Strip [8] and in Tunisia [6]. Moreover, we searched for the Mediterranean allele in the Angolan sample since there are historical references to European populations having settled in Angola, in particular the Portuguese, where this mutation is prevalent [7]. However, we did not encounter the allele in our sample.…”

“…These variants reflect allelic genes located in the long arm of the X chromosome (Xq28) resulting in an X-linked recessive mode of inheritance [7,8]. More than 160 mutations have been identified as responsible for the deficiency, the majority of them consisting of single point mutations causing the replacement of amino acids [6].…”