title: Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes.
abstract: The six types of pattern recognition molecules (PRMs) that initiate complement via the lectin pathway (LP) comprise collectins and ficolins. The importance of having various PRMs to initiate the LP is currently unclear. Mannan-binding lectin (MBL) is a collectin member of the LP PRMs. MBL deficiency is common with mild clinical consequence. Thus, the lack of MBL may be compensated for by the other PRMs. We hypothesized that variants FCN2 + 6424 and FCN3 + 1637delC that cause gene-dose-dependent reduction in ficolin-2 and ficolin-3 levels, respectively, may be rare in MBL-deficient individuals due to the importance of compensation within the LP. The aim of this study was to investigate the distribution and frequency of these variants among MBL2 genotypes in healthy subjects. The allele frequency of FCN2 + 6424 and FCN3 + 1637delC was 0.099 and 0.015, respectively, in the cohort (n = 498). The frequency of FCN2 + 6424 tended to be lower among MBL-deficient subjects (n = 53) than among MBL-sufficient subjects (n = 445) (0.047 versus 0.106, P = 0.057). In addition, individuals who were homozygous for FCN2 + 6424 were sufficient MBL producers. The frequency of FCN3 + 1637delC did not differ between the groups. The frequency of FCN2 + 6424 was similar in FCN3 + 1637delC carriers (n = 15) versus wild type (n = 498). Furthermore, subjects that were heterozygote carriers of both FCN2 + 6424 and FCN3 + 1637delC were sufficient MBL producers. In conclusion, FCN2 + 6424 carriers with MBL deficiency tend to be rare among healthy individuals. MBL-deficient individuals with additional LP PRM defects may be at risk to morbidity.
authors.affiliation: Department of Immunology, Landspitali-The National University Hospital of Iceland, Hringbraut (Building 14 at Eiriksgata), 101, Reykjavik, Iceland. hbjarna@landspitali.is.
authors.forename: Helga
authors.identifier: 0000-0003-3240-3149
authors.initials: H
authors.lastname: Bjarnadottir
authors.affiliation: Department of Immunology, Landspitali-The National University Hospital of Iceland, Hringbraut (Building 14 at Eiriksgata), 101, Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Margret
authors.initials: M
authors.lastname: Arnardottir
authors.affiliation: Department of Immunology, Landspitali-The National University Hospital of Iceland, Hringbraut (Building 14 at Eiriksgata), 101, Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Bjorn Runar
authors.initials: BR
authors.lastname: Ludviksson
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult; D000097604:Ficolins
chemical_list: D006023:Glycoproteins; D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins; C109662:FCN3 protein, human; C445619:MBL2 protein, human
keywords: Complement; FCN2 + 6424; FCN3 + 1637delC; Ficolin-2; Ficolin-3; Lectin pathway; MASP-2; MBL2 genotypes; Mannan-binding lectin; Redundancy