A Population Survey of the Glucose-6-Phosphate Dehydrogenase (G6PD) 563C>T (Mediterranean) Mutation in Afghanistan

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzyme defect and an important problem in areas with Plasmodium vivax infection because of the risk of haemolysis following administration of primaquine to treat the liver forms of the parasite. We undertook a genotypic survey of 713 male individuals across nine provinces of Afghanistan in which malaria is found, four in the north and five in the east. RFLP typing at nucleotide position 563 detected 40 individuals with the Mediterranean mutation 563C>T, an overall prevalence of 5.6%. This varied according to self-reported ethnicity, with prevalence in the Pashtun/Pashai group of 33/369 (8.9%) compared to 7/344 individuals in the rest of the population (2.0%; p<0.001, Chi-squared test). Multivariate analysis of ethnicity and geographical location indicated an adjusted odds ratio of 3.50 (95% CI 1.36–9.02) for the Pashtun/Pashai group, while location showed only a trend towards higher prevalence in eastern provinces (adjusted odds ratio = 1.73, 0.73–4.13). Testing of known polymorphic markers (1311C>T in exon 11, and C93T in intron XI) in a subset of 82 individuals wild-type at C563 revealed a mixture of 3 haplotypes in the background population and was consistent with data from the 1000 Genomes Project and published studies. By comparison individuals with G6PD deficiency showed a highly skewed haplotype distribution, with 95% showing the CT haplotype, a finding consistent with relatively recent appearance and positive selection of the Mediterranean variant in Afghanistan. Overall, the data confirm that the Mediterranean variant of G6PD is common in many ethnic groups in Afghanistan, indicating that screening for G6PD deficiency is required in all individuals before radical treatment of P. vivax with primaquine.

Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World

“…A comparison between the mutations in Arabs and Asians showed that most of the mutations responsible for the G6PDD shared among the two ethnic groups, which could be due to the long history of admixture among the two ethnic groups. These mutations were also shared with other ethnic groups, for example, the most frequent mutation among Arabs, p.S188F, was also frequently reported in Greece, southern Italy, Spain, Bulgaria, Romania, Turkey, and Israel14151617. We identified the most frequent mutations (p.S188F, p.V68M, p.I48T and p.N126D) and unique mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) circulated among Arabs.…”

Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria

“…G6PD gene sequencing was performed with seven pairs of primers designed to amplify all G6PD coding regions for direct DNA sequencing [17–19]. The two silent polymorphic markers, 1311C>T [20] and IVSXI C93T [21], were assessed by amplification of exon 11 and 12 along with introns 11 and 12, as previously described [19, 22]. DNA sequences were assessed by direct sequencing of the PCR product (Macrogen, Seoul, Korea) and analysed with BioEdit bioinformatics programme [365] using NCBI Reference Sequence X55448.1 as G6PD reference.…”

Epidemiology and Control of Plasmodium vivax in Afghanistan

“…If the gold standard treatment includes antirelapse therapy (primaquine), then almost none of Afghanistan's vivax malaria cases are adequately treated because of the absence of G6PD testing. G6PD deficiency is high in certain ethnic groups (up to 10% amongst male ethnic Pashtuns), and about 4% at the population level 25,26. The predominant G6PD genotype is the Mediterranean subtype, which is moderate to severe in the presence of hamolytic factors (e.g., primaquine, dapsone).…”