title: Coding and non-coding polymorphisms in the lectin pathway activator L-ficolin gene in 188 Dutch blood bank donors.
abstract: Human L-ficolin (FCN) is a serum lectin characterized by a collagen-like and a fibrinogen-like domain that can activate the lectin pathway of complement. Structural and functional similarities to mannose-binding lectin (MBL) suggest a role for L-ficolin in innate immunity. Structural polymorphisms in the MBL2 gene lead to functional deficiency of MBL. Polymorphisms in the FCN2 gene have not been studied previously. We developed 10 denaturing gradient gel electrophoresis (DGGE) assays to screen a total of 188 Dutch Caucasians for polymorphisms in FCN2. Total gene screening in this large cohort revealed 10 single nucleotide polymorphisms (SNPs). Interestingly, two conserved coding SNPs were found in exon 8, leading to amino acid substitutions within the fibrinogen-like domain. Fibrinogen-like domains are highly conserved among several proteins in many species. As this domain is responsible for binding of L-ficolin, these newly found coding polymorphisms could alter the affinity of the protein for its substrates and possibly alter the ability of L-ficolin to recognize invading microorganisms.
authors.affiliation: St. Antonius Hospital Nieuwegein, Department of Medical Microbiology and Immunology, P.O. Box 2500, 3430 EM Nieuwegein, Netherlands. b.herpers@antonius.net
authors.forename: Bjorn Lars
authors.initials: BL
authors.lastname: Herpers
authors.forename: Marie-Monique
authors.initials: MM
authors.lastname: Immink
authors.forename: Ben A W
authors.initials: BA
authors.lastname: de Jong
authors.forename: Heleen
authors.initials: H
authors.lastname: van Velzen-Blad
authors.forename: Bartelt M
authors.initials: BM
authors.lastname: de Jongh
authors.forename: Erik J
authors.initials: EJ
authors.lastname: van Hannen
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D001771:Blood Banks; D001782:Blood Donors; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics*; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008403:Mass Screening / Q000379:methods*; D009426:Netherlands; D009691:Nucleic Acid Denaturation; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000097604:Ficolins
chemical_list: D004247:DNA; D037102:Lectins; D000097604:Ficolins