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Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Lea Munthe-Fog
  • Tina Hummelshøj
  • Ying Jie Ma
  • Bjarke E Hansen
  • Claus Koch
  • Hans O Madsen
  • Karsten Skjødt
  • Garred, Peter
Ficolin-3 (Hakata antigen or H-ficolin) is a soluble pattern recognition molecule in the lectin complement pathway. We speculated whether common genetic variations in the FCN3 gene contribute to deficiency of Ficolin-3. The FCN3 gene was sequenced in 237 healthy Danish Caucasians. The relevance of polymorphisms was assessed with antibodies against Ficolin-3 in a novel ELISA system and by production of recombinant Ficolin-3 variants. Ficolin-3 serum profiles were analyzed by SDS-PAGE and western blotting. Ficolin-3 serum concentration varied 10-fold (median, 24microg/ml; range, 3-54microg/ml). Out of several polymorphisms one FCN3+1637delC causing a reading frame shift and a distortion of the C-terminal end of the molecule with an allele frequency of 0.011 was particularly interesting. In individuals heterozygous for the FCN3+1637delC deletion lowered Ficolin-3 concentration was observed (P=0.025). SDS-PAGE and western blotting of serum revealed a weak band corresponding to the truncated molecule in addition to the normal Ficolin-3 pattern. Characterization of recombinant Ficolin-3 derived from FCN3+1637delC showed that in the homozygous situation this allelic variant would lead to Ficolin-3 deficiency. In conclusion an FCN3+1637delC deletion variant disrupting the possibility for pattern recognition was detected. Characterization of recombinant variant Ficolin-3 shows that homozygosity for the FCN3+1637delC deletion may lead to Ficolin-3 deficiency and may thus be the basis for a novel complement deficiency state
Udgivelsesdato: 2008/5
OriginalsprogEngelsk
TidsskriftMolecular Immunology
Vol/bind45
Udgave nummer9
Sider (fra-til)2660-2666
Antal sider6
ISSN0161-5890
DOI
StatusUdgivet - 2008

ID: 10209251