Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state
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Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state. / Munthe-Fog, Lea; Hummelshøj, Tina; Ma, Ying Jie; Hansen, Bjarke E; Koch, Claus; Madsen, Hans O; Skjødt, Karsten; Garred, Peter.
I: Molecular Immunology, Bind 45, Nr. 9, 2008, s. 2660-2666.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state
AU - Munthe-Fog, Lea
AU - Hummelshøj, Tina
AU - Ma, Ying Jie
AU - Hansen, Bjarke E
AU - Koch, Claus
AU - Madsen, Hans O
AU - Skjødt, Karsten
AU - Garred, Peter
N1 - Keywords: Adult; Cell Line; Enzyme-Linked Immunosorbent Assay; Exons; Glycoproteins; Heterozygote; Homozygote; Humans; Lectins; Polymorphism, Genetic; Promoter Regions, Genetic; Recombinant Proteins; Sequence Analysis, DNA
PY - 2008
Y1 - 2008
N2 - 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
AB - 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
U2 - 10.1016/j.molimm.2007.12.012
DO - 10.1016/j.molimm.2007.12.012
M3 - Journal article
C2 - 18261799
VL - 45
SP - 2660
EP - 2666
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 9
ER -
ID: 10209251