Authors:
, , , , , , , , , , , , , , , , , and
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-
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.
-
2.
Luzzatto L, 2012. G6PD deficiency and malaria selection. Heredity (Edinb) 108: 456.
-
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: 455–462.
-
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: 107–110.
-
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.
-
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: 246–249.
-
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.
-
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: 31–36.
-
9.
Ademowo OG, Falusi AG, 2002. Molecular epidemiology and activity of erythrocyte G6PD variants in a homogeneous Nigerian population. East Afr Med J 79: 42–44.
-
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: 119–123.
-
11.
Beutler E, Kuhl W, Vives-Corrons JL, Prchal JT, 1989. Molecular heterogeneity of glucose-6-phosphate dehydrogenase A-. Blood 74: 2550–2555.
-
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.
-
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: 262–263.
-
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: 1080–1085.
-
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.
-
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: 249–259.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1443 | 1306 | 401 |
| Full Text Views | 596 | 17 | 1 |
| PDF Downloads | 244 | 19 | 3 |
G6PD A- Deficiency and Severe Malaria in The Gambia: Heterozygote Advantage and Possible Homozygote Disadvantage
Giorgio Sirugo
Giorgio Sirugo
Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; Medical Research Council Laboratories, Fajara, Banjul, The Gambia
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Irene M. Predazzi
Irene M. Predazzi
Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; Medical Research Council Laboratories, Fajara, Banjul, The Gambia
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Jacquelaine Bartlett
Jacquelaine Bartlett
Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; Medical Research Council Laboratories, Fajara, Banjul, The Gambia
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Alessandra Tacconelli
Alessandra Tacconelli
Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; Medical Research Council Laboratories, Fajara, Banjul, The Gambia
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Michael Walther
Michael Walther
Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; Medical Research Council Laboratories, Fajara, Banjul, The Gambia
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Scott M. Williams
Scott M. Williams
Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; Medical Research Council Laboratories, Fajara, Banjul, The Gambia
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is frequent in Africa, because it confers resistance to Plasmodium falciparum 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 (G6PD 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.
Author Notes
Authors' addresses: Giorgio Sirugo and Alessandra Tacconelli, Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy, E-mails: sirugo.giorgio@fbfrm.it and alessandra.tacconelli@gmail.com. Irene M. Predazzi, Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, E-mail: irene.m.predazzi@vanderbilt.edu. Jacquelaine Bartlett and Scott M. Williams, Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, E-mail: Jacquelaine.Bartlett@dartmouth.edu and Scott.Williams@dartmouth.edu. Michael Walther, National Institute of Allergy and Infectious Diseases, National Institutes of Health Laboratory of Malaria Immunology and Vaccinology, Rockville, MD, E-mail: michael.walther@nih.gov.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
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.
-
2.
Luzzatto L, 2012. G6PD deficiency and malaria selection. Heredity (Edinb) 108: 456.
-
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: 455–462.
-
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: 107–110.
-
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.
-
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: 246–249.
-
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.
-
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: 31–36.
-
9.
Ademowo OG, Falusi AG, 2002. Molecular epidemiology and activity of erythrocyte G6PD variants in a homogeneous Nigerian population. East Afr Med J 79: 42–44.
-
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: 119–123.
-
11.
Beutler E, Kuhl W, Vives-Corrons JL, Prchal JT, 1989. Molecular heterogeneity of glucose-6-phosphate dehydrogenase A-. Blood 74: 2550–2555.
-
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.
-
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: 262–263.
-
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: 1080–1085.
-
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.
-
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: 249–259.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1443 | 1306 | 401 |
| Full Text Views | 596 | 17 | 1 |
| PDF Downloads | 244 | 19 | 3 |