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

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.