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

• Published in: Genes & Immunity
• Main Authors: Thiel, S, Steffensen, R, Christensen, I J, Ip, W K, Lau, Y L, Reason, I J M, Eiberg, Hans Rudolf Lytchoff, Gadjeva, M, Ruseva, M, Jensenius, Jens Christian
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2007
• Subjects: African Continental Ancestry Group; Asian Continental Ancestry Group; Brazil; DNA Primers; Exons; Gene Frequency; Genotype; Greenland; Hong Kong; Humans; Indians; South American; Inuits; Mannose-Binding Protein-Associated Serine Proteases; Mutation; Missense; Polymorphism; Genetic; Sequence Analysis; DNA; Zambia; inuits
• Online Access: https://pure.au.dk/portal/da/publications/deficiency-of-mannanbinding-lectin-associated-serine-protease2-due-to-missense-polymorphisms(2b735bf3-f138-44ef-bc84-776b18f55ff7).html; https://doi.org/10.1038/sj.gene.6364373

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.