title: Glucose-6-phosphate dehydrogenase deficient variants are associated with reduced susceptibility to malaria in the Brazilian Amazon.
abstract: BACKGROUND
  Glucose-6-phosphate dehydrogenase deficiency (G6PDd) has been shown to protect against malaria infection and severe manifestations in African and Asia, but there is a scarcity of studies in the Americas. This study aimed to study the prevalence of G6PDd and its association with malaria occurrence in the Brazilian Amazon.
  
  
  METHODS
  A cross-sectional study was conducted in the male population to estimate the prevalence of G6PDd and malaria infection. G6PD deficient samples were genotyped to identify the deficient variant. Number of previous malaria episodes and need for blood transfusion during malaria episodes were recorded by applying a standardized questionary.
  
  
  RESULTS
  From a sample of 1478 male individuals, 66 were detected as G6PD deficient, resulting in a prevalence of of 4.5% (95% CI = 3.44-5.56%). Fifty six G6PD deficient individuals (3.8%; 95% CI = 2.82-4.77) presented the G6PD A-variant mutation, while 10 individuals (0.7%; 95% CI = 0.42-0.97) severely deficient were genotyped as carriers of the G6PD Mediterranean variant. After adjusting for age, G6PD deficient individuals were less likely to report the occurrence of malaria episodes, and the protective effect was related to the enzyme activity, with carriers of the GG6PD A-variant presenting a 88% reduction (AOR: 0.119; 95% CI = 0.057-0.252; p < 0.001) and carriers of the Meditarrenean variant presenting 99% lower risk (AOR: 0.010; 95% CI = 0.002-0.252; p < 0.001) when compared to non-deficient individuals. On the other hand, G6PD deficient subjects reported higher need of transfusion during malaria episodes (p < 0.001).
  
  
  CONCLUSIONS
  G6PD enzyme activity was directly related to susceptibility to malaria in the Brazilian Amazon, where P. vivax predominates. Severe G6PDd was associated with considerable higher risk of malaria-related transfusions.
authors.affiliation: Universidade do Estado do Amazonas, Av Pedro Teixeira, 25 Dom Pedro, 69040-000 Manaus, Amazonas, Brazil.
authors.forename: Marli S
authors.initials: MS
authors.lastname: Santana
authors.forename: Wuelton M
authors.initials: WM
authors.lastname: Monteiro
authors.forename: André M
authors.initials: AM
authors.lastname: Siqueira
authors.forename: Mônica F
authors.initials: MF
authors.lastname: Costa
authors.forename: Vanderson
authors.initials: V
authors.lastname: Sampaio
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Lacerda
authors.forename: Maria G
authors.initials: MG
authors.lastname: Alecrim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004198:Disease Susceptibility; D014644:Genetic Variation; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007843:Latin America / Q000453:epidemiology; D008288:Malaria / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011319:Primaquine; D055815:Young Adult
chemical_list: D011319:Primaquine