title: G6PD A- deficiency and severe malaria in The Gambia: heterozygote advantage and possible homozygote disadvantage.
abstract: 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.
authors.affiliation: 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.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sirugo
authors.forename: Irene M
authors.initials: IM
authors.lastname: Predazzi
authors.forename: Jacquelaine
authors.initials: J
authors.lastname: Bartlett
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tacconelli
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005714:Gambia / Q000453:epidemiology; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006790:Host-Parasite Interactions; D006801:Humans; D007223:Infant; D016015:Logistic Models; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics; D008297:Male
chemical_list: D017931:DNA Primers; D005954:Glucosephosphate Dehydrogenase; C482910:glucose-6-phosphate dehydrogenase A-