title: Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria.
abstract: BACKGROUND
  Innate immunity plays a crucial role in the host defense against malaria including Plasmodium falciparum malaria in pregnancy, but the roles of the various underlying genes and mechanisms predisposing to the disease are poorly understood.
  
  
  METHODS
  98 single-nucletoide polymorphisms were genotyped in a set of 17 functionally related genes of the complement system in 145 primiparous Ghanaian women with placental malaria, defined by placental parasitaemia or malaria pigment, and as a control, in 124 non-affected primiparae.
  
  
  RESULTS
  Placental malaria was significantly associated with SNPs in the lectin pathway genes MBL2, MASP2, FCN2 and in properdin. In particular, the main African mannose-binding lectin deficiency variant (MBL2*G57E, rs1800451) increased the odds of placental malaria (OR 1.6; permuted p-value 0.014). In contrast, a common MASP2 mutation (R439H, rs12085877), which reduces the activity of MBL-MASP2 complexes occurred in 33% of non-affected women and in 22% primiparae with placental malaria (OR 0.55, permuted p-value 0.020).
  
  
  CONCLUSIONS
  Excessive complement activation is of importance in the pathogenesis of placental malaria by mediating inflammation, coagulation, and endothelial dysfunction. Mutated MBL and MASP2 proteins could have direct intrinsic effects on the susceptibility to placental malaria, in addition to their roles in regulation of downstream complement activation.
authors.affiliation: Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland. ville.holmberg@helsinki.fi
authors.forename: Ville
authors.initials: V
authors.lastname: Holmberg
authors.forename: Päivi
authors.initials: P
authors.lastname: Onkamo
authors.forename: Elisa
authors.initials: E
authors.lastname: Lahtela
authors.forename: Päivi
authors.initials: P
authors.lastname: Lahermo
authors.forename: George
authors.initials: G
authors.lastname: Bedu-Addo
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
mesh_terms: D000328:Adult; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D005869:Ghana; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000276:immunology; D010920:Placenta / Q000276:immunology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000235:genetics* / Q000276:immunology / Q000469:parasitology
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D003165:Complement System Proteins; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases