title: Population genetics of GYPB and association study between GYPB*S/s polymorphism and susceptibility to P. falciparum infection in the Brazilian Amazon.
abstract: BACKGROUND
  Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil.
  
  
  METHODS
  Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection.
  
  
  RESULTS
  GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity.
  
  
  CONCLUSIONS
  Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tarazona-Santos
authors.forename: Lilian
authors.initials: L
authors.lastname: Castilho
authors.forename: Daphne R T
authors.initials: DR
authors.lastname: Amaral
authors.forename: Daiane C
authors.initials: DC
authors.lastname: Costa
authors.forename: Natália G
authors.initials: NG
authors.lastname: Furlani
authors.forename: Luciana W
authors.initials: LW
authors.lastname: Zuccherato
authors.forename: Moara
authors.initials: M
authors.lastname: Machado
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
authors.forename: Mariano G
authors.initials: MG
authors.lastname: Zalis
authors.forename: Andréa R
authors.initials: AR
authors.lastname: Rossit
authors.forename: Sidney E B
authors.initials: SE
authors.lastname: Santos
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Machado
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
mesh_terms: D000483:Alleles; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D019353:Endemic Diseases; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006021:Glycophorins / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics*; D010963:Plasmodium falciparum / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: C409973:GYPB protein, human; D005819:Genetic Markers; D006021:Glycophorins