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

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

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.

Afiliação

Thiel S; Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. st@microbiology.au.dk

Genes Immun ; 8(2): 154-63, 2007 Mar.

Article em En | MEDLINE | ID: mdl-17252003

RESUMO

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.

Assuntos

Povo Asiático/genética; População Negra/genética; Indígenas Sul-Americanos/genética; Inuíte/genética; Serina Proteases Associadas a Proteína de Ligação a Manose/deficiência; Serina Proteases Associadas a Proteína de Ligação a Manose/genética; Polimorfismo Genético; Brasil; Primers do DNA; Éxons/genética; Frequência do Gene; Genótipo; Groenlândia; Hong Kong; Humanos; Mutação de Sentido Incorreto/genética; Análise de Sequência de DNA; Zâmbia

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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Inuíte / Indígenas Sul-Americanos / População Negra / Povo Asiático / Serina Proteases Associadas a Proteína de Ligação a Manose Tipo de estudo: Risk_factors_studies Limite: Humans País/Região como assunto: Africa / America do norte / America do sul / Asia / Brasil / Europa Idioma: En Revista: Genes Immun Assunto da revista: ALERGIA E IMUNOLOGIA / BIOLOGIA MOLECULAR Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Dinamarca País de publicação: Reino Unido

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