Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation

Genes Immun. 2012 Oct;13(7):515-22. doi: 10.1038/gene.2012.27. Epub 2012 Jun 7.

Abstract

Ficolin-1 is a recognition molecule of the lectin complement pathway. The ficolin-1 gene FCN1 is polymorphic, but the functional and clinical consequences are unknown.The concentration of ficolin-1 in plasma and FCN1 polymorphisms in positions -1981 (rs2989727), -791 (rs28909068), -542 (rs10120023), -271 (rs28909976), -144 (rs10117466) and +7918 (rs1071583) were determined in 100 healthy individuals. FCN1 expression by isolated monocytes and granulocytes and ficolin-1 levels in monocyte culture supernatants were assessed in 21 FCN1-genotyped individuals. FCN1 polymorphisms were determined in a cohort of 251 patients with systemic inflammation. High ficolin-1 plasma levels were significantly associated with the minor alleles in position -542 and -144. These alleles were also significantly associated with high FCN1 mRNA expression. The level of ficolin-1 in culture supernatants was significantly higher in individuals homozygous for the minor alleles at positions -542 and -144. Homozygosity for these alleles was significantly associated with fatal outcome in patients with systemic inflammation. None of the other investigated polymorphisms were associated with FCN1 and ficolin-1 expression, concentration or disease outcome. Functional polymorphic sites in the promoter region of FCN1 regulate both the expression and synthesis of ficolin-1 and are associated with outcome in severe inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Gene Expression
  • Gene Frequency
  • Homozygote
  • Humans
  • Lectins / biosynthesis
  • Lectins / blood
  • Lectins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • RNA, Messenger / biosynthesis
  • Systemic Inflammatory Response Syndrome / genetics*
  • Systemic Inflammatory Response Syndrome / mortality

Substances

  • Lectins
  • RNA, Messenger
  • ficolin