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

S. Thiel, R. Steffensen, I. J. Christensen, W. K. Ip, Y. L. Lau, I. J.M. Reason, H. Eiberg, M. Gadjeva, M. Ruseva, J. C. Jensenius

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63 Scopus citations

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, 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.

Original languageEnglish (US)
Pages (from-to)154-163
Number of pages10
JournalGenes and Immunity
Volume8
Issue number2
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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    Thiel, S., Steffensen, R., Christensen, I. J., Ip, W. K., Lau, Y. L., Reason, I. J. M., Eiberg, H., Gadjeva, M., Ruseva, M., & Jensenius, J. C. (2007). Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes and Immunity, 8(2), 154-163. https://doi.org/10.1038/sj.gene.6364373