Non-synonymous polymorphisms in the FCN1 gene determine ligand-binding ability and serum levels of M-ficolin

PLoS One. 2012;7(11):e50585. doi: 10.1371/journal.pone.0050585. Epub 2012 Nov 28.


Background: The innate immune system encompasses various recognition molecules able to sense both exogenous and endogenous danger signals arising from pathogens or damaged host cells. One such pattern-recognition molecule is M-ficolin, which is capable of activating the complement system through the lectin pathway. The lectin pathway is multifaceted with activities spanning from complement activation to coagulation, autoimmunity, ischemia-reperfusion injury and embryogenesis. Our aim was to explore associations between SNPs in FCN1, encoding M-ficolin and corresponding protein concentrations, and the impact of non-synonymous SNPs on protein function.

Principal findings: We genotyped 26 polymorphisms in the FCN1 gene and found 8 of these to be associated with M-ficolin levels in a cohort of 346 blood donors. Four of those polymorphisms were located in the promoter region and exon 1 and were in high linkage disequilibrium (r(2)≥0.91). The most significant of those were the AA genotype of -144C>A (rs10117466), which was associated with an increase in M-ficolin concentration of 26% compared to the CC genotype. We created recombinant proteins corresponding to the five non-synonymous mutations encountered and found that the Ser268Pro (rs150625869) mutation lead to loss of M-ficolin production. This was backed up by clinical observations, indicating that an individual homozygote of Ser268Pro would be completely M-ficolin deficient. Furthermore, the Ala218Thr (rs148649884) and Asn289Ser (rs138055828) were both associated with low M-ficolin levels, and the mutations crippled the ligand-binding capability of the recombinant M-ficolin, as indicated by the low binding to Group B Streptococcus.

Significance: Overall, our study interlinks the genotype and phenotype relationship concerning polymorphisms in FCN1 and corresponding concentrations and biological functions of M-ficolin. The elucidations of these associations provide information for future genetic studies in the lectin pathway and complement system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Female
  • Genotype
  • Humans
  • Lectins / blood
  • Lectins / genetics*
  • Lectins / metabolism*
  • Male
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Protein Binding
  • Sex Factors


  • Lectins
  • ficolin

Grants and funding

This work received the following grant support: The Danish Rheumatism Association (, The Fonden til Lægevidenskabens Fremme (, The Hede Nielsen Foundation (, The Aase and Ejnar Danielsens Foundation ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.