1. ¹Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark
2. ²Regional Centre for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
3. ³Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark
4. ⁴Department of Pediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong, China
5. ⁵Department of Clinical Pathology, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil
6. ⁶Department of Medical Biochemistry and Genetics, Panum Institute, Copenhagen, Denmark

Correspondence: Dr S Thiel, Department of Medical Microbiology and Immunology, University of Aarhus, Bartholin Building, 8000 Aarhus, Denmark. E-mail: st@microbiology.au.dk

Received 7 September 2006; Revised 12 December 2006; Accepted 13 December 2006; Published online 25 January 2007.

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.