title: Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms.
abstract: Mannan-binding lectin (MBL) and ficolins distinguish between self, non-self and altered-self by recognizing patterns of ligands on the surface of microorganisms or aberrant cells. When this happens MBL-associated serine protease-2 (MASP-2) is activated and cleaves complement factors to start inflammatory actions. We examined human populations for MASP-2 levels, MASP-2 function and for the presence of mutations in coding exons of MASP2. The MASP-2 levels were lowest in Africans from Zambia (median, 196 ng/ml) followed by Hong Kong Chinese (262 ng/ml), Brazilian Amerindians (290 ng/ml) and Danish Caucasians (416 ng/ml). In the Chinese population, we uncovered a novel four amino-acid tandem duplication (p.156_159dupCHNH) associated with low levels of MASP-2. The frequency of this mutation as well as the SNPs p.R99C, p.R118C, p.D120G, p.P126L and p.V377A were analyzed. The p.156_159dupCHNH was only found in Chinese (gene frequency 0.26%) and p.D120G was found only in Caucasians and Inuits from West-Greenland. The p.P126L and p.R99Q were present in Africans and Amerindians only, except for p.R99Q in one Caucasian. The MASP-2 levels were reduced in individuals with p.V377A present. The MASP-2 present in individuals homozygous for p.377A or p.99Q had a normal enzyme activity whereas MASP-2 in individuals homozygous for p.126L was non-functional.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. st@microbiology.au.dk
authors.forename: S
authors.initials: S
authors.lastname: Thiel
authors.forename: R
authors.initials: R
authors.lastname: Steffensen
authors.forename: I J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: W K
authors.initials: WK
authors.lastname: Ip
authors.forename: Y L
authors.initials: YL
authors.lastname: Lau
authors.forename: I J M
authors.initials: IJ
authors.lastname: Reason
authors.forename: H
authors.initials: H
authors.lastname: Eiberg
authors.forename: M
authors.initials: M
authors.lastname: Gadjeva
authors.forename: M
authors.initials: M
authors.lastname: Ruseva
authors.forename: J C
authors.initials: JC
authors.lastname: Jensenius
mesh_terms: D044466:Asian People / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D001938:Brazil; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006116:Greenland; D006723:Hong Kong; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D004930:Inuit / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000172:deficiency* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D015024:Zambia
chemical_list: D017931:DNA Primers; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases