X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria.

Article English OPEN
Aldiouma Guindo ; Rick M Fairhurst ; Ogobara K Doumbo ; Thomas E Wellems ; Dapa A Diallo (2007)
  • Publisher: Public Library of Science (PLoS)
  • Journal: PLoS Medicine, volume 4, issue 3 (issn: 1549-1277, eissn: 1549-1676)
  • Related identifiers: pmc: PMC1820604, doi: 10.1371/journal.pmed.0040066
  • Subject: Research Article | Infectious Diseases | Microbiology | Medicine | Malaria | Epidemiology | Hematology | R | Evolutionary Biology | Genetics | Public Health and Epidemiology | Hematology (including Blood Transfusion)
    mesheuropmc: hemic and lymphatic diseases | parasitic diseases

Editors' Summary Background. “Favism” is a condition that results from a deficiency in an enzyme called glucose-6-phosphate dehydrogenase (G6PD), and this disorder is thought to be the commonest enzyme-deficiency disease worldwide. The disease is named favism after the Italian word for broad beans (fava), which cause a classic reaction when eaten by people with G6PD deficiency. The G6PD enzyme is particularly important in red blood cells, where it protects against damage that can be caused by certain drugs or other stresses. There are a number of normal variants of G6PD, with G6PD A and G6PD B being common in Africa. However, abnormal mutations in the gene can lead to anemia as a result of the red blood cells breaking down in response to certain drugs or types of food, or in other situations. G6PD deficiency is not spread evenly around the world; it is particularly common in Africa and the Mediterranean, and up to 20%–25% of people in certain African regions can have the condition. Although there can be serious clinical outcomes from G6PD deficiency that result from the red blood cells being broken down, G6PD deficiency may protect against malaria. Why Was This Study Done? The researchers here wanted to find out whether, in regions where virtually all children get malaria during early childhood, a mutation in G6PD A (written as G6PD A−) that leads to G6PD deficiency protects children from having their malaria episodes worsen into severe, life-threatening disease. They also wanted to look at whether the degree of protection from G6PD A− deficiency differed between boys and girls. The reason for looking at this had to do with the genetics of G6PD deficiency. The gene coding for G6PD is carried on the X chromosome, of which males have only one copy, whereas females have two. Therefore, males will be G6PD deficient when they inherit only one mutant gene, but females need to inherit two abnormal genes (or have the normal gene turned off, which happens by a process known as X-inactivation in a proportion of female cells). What Did the Researchers Do and Find? This study was carried out in two regions of Mali, West Africa, where malaria affects virtually all children under the age of 5 years. The children recruited at each study site came from two distinct cultural groups, the Dogon people of Bandiagara and the Malinké people of Kangaba and Kela. The researchers studied children coming to the medical clinics in each area with either uncomplicated malaria (i.e., mild symptoms) or severe malaria. All patients were treated normally according to the standard practices for this region. Blood samples were collected from each child in order to see how many malaria parasites were in the blood, as well as to analyze each patient's DNA to work out whether they had a mutant form of the G6PD*A gene that causes the G6PD A− form of deficiency. Overall, 3,197 children were recruited into the study, 2,765 of whom had uncomplicated malaria and 432 had severe malaria. In both ethnic groups, children with severe malaria were much less likely to have the mutant form of the G6PD*A gene than children with uncomplicated malaria, showing that the gene mutation protected children from having their malaria progress to severe malaria. The researchers then looked at whether the protection given by the mutant forms of G6PD affected boys and girls differently. The researchers found that protection against severe malaria occurred in boys but not girls who had inherited one mutant G6PD*A− gene. What Do These Findings Mean? These data show that the mutation in G6PD*A that leads to the G6PD A− deficiency gives children substantial protection against severe malaria, but this protection seems to be the case for boys and not girls who have only one mutant copy of the gene. There seems to be around a two-thirds drop in risk of severe malaria in boys with G6PD deficiency as compared to normal boys. At present the reason for this difference in protection is not clear, because it is not known how malaria parasites are affected by red blood cells that lack G6PD activity. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040066. Medline Plus has an article on glucose-6-phosphate dehydrogenase deficiency Wikipedia has an entry on glucose-6-phosphate dehydrogenase deficiency (Wikipedia is a free internet encyclopedia that anyone can edit) Information on malaria is available from the US Centers for Disease Control
Share - Bookmark