1921
Volume 90, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is frequent in Africa, because it confers resistance to malaria; however, the nature of the protection and the genotypes associated with it have been controversial. In 1972, Bienzle and others described protection from malaria in West African females heterozygous for G6PD A-. They determined that G6PD A- heterozygotes had lower parasite counts than A- homozygotes, hemizygous males, and normal individuals. However, other studies have reached different conclusions about the protective genotypes. DNA samples from 135 children with severe malaria and 146 children with mild malaria from The Gambia were genotyped for the G6PD A- mutation that is most frequent among Gambians ( 968 T->C); there was a marked deficiency of heterozygotes and an excess of homozygotes with severe malaria, producing a strong deviation from Hardy–Weinberg equilibrium. Our results support the protective effect in G6PD A- heterozygous females and suggest that homozygotes might be more susceptible to severe malaria attacks.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.13-0622
2014-05-07
2017-09-20
Loading full text...

Full text loading...

/deliver/fulltext/14761645/90/5/856.html?itemId=/content/journals/10.4269/ajtmh.13-0622&mimeType=html&fmt=ahah

References

  1. Howes RE, Piel FB, Patil AP, Nyangiri OA, Gething PW, Dewi M, Hogg MM, Battle KE, Padilla CD, Baird JK, Hay SI, , 2012. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med 9: e1001339.[Crossref]
  2. Luzzatto L, , 2012. G6PD deficiency and malaria selection. Heredity (Edinb) 108: 456.[Crossref]
  3. Tishkoff SA, Varkonyi R, Cahinhinan N, Abbes S, Argyropoulos G, Destro-Bisol G, Drousiotou A, Dangerfield B, Lefranc G, Loiselet J, Piro A, Stoneking M, Tagarelli A, Tagarelli G, Touma EH, Williams SM, Clark AG, , 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293: 455462.[Crossref]
  4. Bienzle U, Ayeni O, Lucas AO, Luzzatto L, , 1972. Glucose-6-phosphate dehydrogenase and malaria. Greater resistance of females heterozygous for enzyme deficiency and of males with non-deficient variant. Lancet 1: 107110.[Crossref]
  5. Guindo A, Fairhurst RM, Doumbo OK, Wellems TE, Diallo DA, , 2007. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med 4: e66.[Crossref]
  6. Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, Warn P, Allsopp CE, Gilbert SC, Peschu N, , 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376: 246249.[Crossref]
  7. Sirugo G, , 2013. Reassessing an old claim: natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Am J Hematol 88: 436.[Crossref]
  8. Battistuzzi G, Esan GJ, Fasuan FA, Modiano G, Luzzatto L, , 1977. Comparison of GdA and GdB activities in Nigerians. A study of the variation of the G6PD activity. Am J Hum Genet 29: 3136.
  9. Ademowo OG, Falusi AG, , 2002. Molecular epidemiology and activity of erythrocyte G6PD variants in a homogeneous Nigerian population. East Afr Med J 79: 4244.[Crossref]
  10. May J, Meyer CG, Grossterlinden L, Ademowo OG, Mockenhaupt FP, Olumese PE, Falusi AG, Luzzatto L, Bienzle U, , 2000. Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population. Trop Med Int Health 5: 119123.[Crossref]
  11. Beutler E, Kuhl W, Vives-Corrons JL, Prchal JT, , 1989. Molecular heterogeneity of glucose-6-phosphate dehydrogenase A-. Blood 74: 25502555.
  12. Hirono A, Kawate K, Honda A, Fujii H, Miwa S, , 2002. A single mutation 202G>A in the human glucose-6-phosphate dehydrogenase gene (G6PD) can cause acute hemolysis by itself. Blood 99: 1498.[Crossref]
  13. De Araujo C, Migot-Nabias F, Guitard J, Pelleau S, Vulliamy T, Ducrocq R, , 2006. The role of the G6PD AEth376G/968C allele in glucose-6-phosphate dehydrogenase deficiency in the seerer population of Senegal. Haematologica 91: 262263.
  14. Clark TG, Fry AE, Auburn S, Campino S, Diakite M, Green A, Richardson A, Teo YY, Small K, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Sabeti P, Kwiatkowski DP, Rockett KA, , 2009. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility. Eur J Hum Genet 17: 10801085.[Crossref]
  15. Walther M, De Caul A, Aka P, Njie M, Amambua-Ngwa A, Walther B, Predazzi IM, Cunnington A, Deininger S, Takem EN, Ebonyi A, Weis S, Walton R, Rowland-Jones S, Sirugo G, Williams SM, Conway DJ, , 2012. HMOX1 gene promoter alleles and high HO-1 levels are associated with severe malaria in Gambian children. PLoS Pathog 8: e1002579.[Crossref]
  16. Rodrigues MO, Freire AP, Martins G, Pereira J, Martins MD, Monteiro C, , 2002. Glucose-6-phosphate dehydrogenase deficiency in Portugal: biochemical and mutational profiles, heterogeneity, and haplotype association. Blood Cells Mol Dis 28: 249259.[Crossref]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.13-0622
Loading
/content/journals/10.4269/ajtmh.13-0622
Loading

Data & Media loading...

  • Received : 25 Oct 2013
  • Accepted : 31 Jan 2014

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error