Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria
1 Department of Bacteriology and Immunology, Infection Biology Programme, Haartman Institute, University of Helsinki, P.O. Box 21, 00014 Helsinki, Finland
2 Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, P.O. Box 340, 00029 HUS Helsinki, Finland
3 Department of Biosciences, University of Helsinki, P.O.Box 56, 00014 Helsinki, Finland
4 FIMM Technology Centre, University of Helsinki, P.O. Box 20, 00014 Helsinki, Finland
5 Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
6 Institute of Tropical Medicine and International Health, Charité-University Medical Center, Spandauer Damm 130, 14050 Berlin, Germany
7 HUSLAB, Helsinki University Central Hospital, Helsinki, Finland
Malaria Journal 2012, 11:61 doi:10.1186/1475-2875-11-61Published: 2 March 2012
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.
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.
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).
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.