title: Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait.
abstract: BACKGROUND
  The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects.
  
  
  METHODS
  Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution.
  
  
  RESULTS
  In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed.
  
  
  CONCLUSIONS
  The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.
authors.affiliation: Unité d'Imunologie Moléculaire des Parasites, Institut Pasteur, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Ntoumi
authors.forename: C
authors.initials: C
authors.lastname: Rogier
authors.forename: A
authors.initials: A
authors.lastname: Dieye
authors.forename: J F
authors.initials: JF
authors.lastname: Trape
authors.forename: P
authors.initials: P
authors.lastname: Millet
authors.forename: O
authors.initials: O
authors.lastname: Mercereau-Puijalon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000032:analysis; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006441:Hemoglobin A / Q000032:analysis*; D006451:Hemoglobin, Sickle / Q000032:analysis*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D008297:Male; D020066:Merozoite Surface Protein 1; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D012675:Senegal / Q000453:epidemiology; D012805:Sickle Cell Trait / Q000097:blood* / Q000150:complications
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D006451:Hemoglobin, Sickle; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C028672:hemoglobin AA; C028671:hemoglobin AS; D006441:Hemoglobin A