title: Association of a new mannose-binding lectin variant with severe malaria in Gabonese children.
abstract: Mannose-binding lectin (MBL2) variants that decrease the plasma level of the protein or encode dysfunctional proteins are frequently associated with the severity of a number of infections and autoimmune disorders. The high frequencies of these variants in most populations of the world are probably maintained by some selective advantage against widespread diseases. We found 14 new MBL2 allelic haplotypes, two of them with non-synonymous variants, by screening 136 children with uncomplicated malaria, 131 children with severe malaria and 39 older healthy schoolchildren. We also found a significant association of a novel variant with susceptibility to severe malaria (P=0.010). Increased MBL plasma levels and corresponding MBL2 genotypes were associated with lower concentration of several cytokines and chemokines in plasma of malaria patients. We suggest that malaria could have been one of the evolutionary driving forces shaping the MBL2 polymorphism in the African population.
authors.affiliation: Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: A B W
authors.initials: AB
authors.lastname: Boldt
authors.forename: A
authors.initials: A
authors.lastname: Luty
authors.forename: M P
authors.initials: MP
authors.lastname: Grobusch
authors.forename: K
authors.initials: K
authors.lastname: Dietz
authors.forename: A
authors.initials: A
authors.lastname: Dzeing
authors.forename: M
authors.initials: M
authors.lastname: Kombila
authors.forename: P G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: J F J
authors.initials: JF
authors.lastname: Kun
mesh_terms: D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D019143:Evolution, Molecular; D005091:Exons; D005681:Gabon / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008288:Malaria / Q000378:metabolism* / Q000473:pathology*; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
chemical_list: D018925:Chemokines; D016207:Cytokines; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin