Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms

• Published in: Genes & Immunity
• Main Authors: Jensenius, JC, Thiel, S, Steffensen, R, Christensen, IJ, Ip, WK, Lau, YL, Reason, IJM, Eiberg, H, Gadjeva, M, Ruseva, M
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group. The Journal's web site is located at http://www.nature.com/gene 2007
• Subjects: African Continental Ancestry Group - Genetics; Asian Continental Ancestry Group - Genetics; Brazil; Dna Primers; Exons - Genetics; Gene Frequency; Genotype; Greenland; Hong Kong; Humans; Indians; South American - Genetics; Inuits - Genetics; Mannose-Binding Protein-Associated Serine Proteases - Deficiency - Genetics; Mutation; Missense - Genetics; Polymorphism; Genetic; Sequence Analysis; Dna; Zambia; inuits
• Online Access: https://doi.org/10.1038/sj.gene.6364373; http://hdl.handle.net/10722/170384

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, 196ng/ml) followed by Hong Kong Chinese (262ng/ml), Brazilian Amerindians (290ng/ml) and Danish Caucasians (416ng/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. link_to_subscribed_fulltext