Human Molecular Genetics Advance Access published online on May 6, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi173
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1 Tissue Typing Laboratory-7631, Department of Clinical Immunology, Rigshospitalet, 2100 Copenhagen, Denmark
* To whom correspondence should be addressed. The ficolin 1, 2 and 3 (derived from the FCN1, 2 and 3 genes, respectively) are homologous soluble pattern recognition molecules of importance for innate immunity, comprising collagen-like and fibrinogen-like domains, binding to sugar groups on different types of microorganisms. Serum concentration of Ficolin-2 varies considerably in healthy individuals. Thus, we speculated whether this could be due to variations in the FCN2 gene. We sequenced the promoter region and the exons and intron-exon boundaries of FCN2 in Danish Caucasians. For comparison FCN1 and FCN3 were also investigated. Ficolin-2 concentrations were measured in serum and the functional relevance of amino acid substituting polymorphisms in FCN2 was investigated by binding to and recovery from N-acetylglucosamine (GlcNAc). Both FCN1 and FCN2 contained polymorphisms in the promoters and structural parts of the genes, but only polymorphisms in FCN2 resulted in amino acid exchanges. FCN2 promoter polymorphisms were associated with marked changes in the Ficolin-2 serum concentration, while two polymorphisms clustered in the exon encoding the fibrinogen-like domain were associated with increased and decreased GlcNAc binding, respectively. In FCN3, only a single frame shift deletion in exon 5 was detected. These results show that the FCN genes are polymorphic and that particularly FCN2 harbour functional polymorphic sites that both regulate the expression as well as the function of Ficolin-2, which may have pathophysiological implications for innate immunity.
Received March 16, 2005
Revised April 26, 2005
Accepted April 26, 2005
Article
Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2
2 Department of Biochemistry, Fukushima Medical University School, Fukushima 960-1295, Japan
3 Institute of Glycotechnology and Department of Applied Biochemistry, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan
4 Tissue Typing Laboratory-7631, Department of Clinical Immunology, Blegdamsvej 9, DK-2100 Copenhagen O, DENMARK
Peter Garred, E-mail: garred{at}post5.tele.dk
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