title: Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns.
abstract: The ficolin protein family comprises three different molecules encoded by the FCN1, FCN2, and FCN3 genes, respectively, that play roles in innate immunity. The FCN genes in Caucasians are polymorphic and genetic variations may have functional consequences both in relation to function and concentration. The ethnic diversity of the FCN genes is unknown. The promoter and coding regions of the FCNs genes were sequenced in individuals from five different ethnic groups: Caucasians (Denmark, n=60), Japanese (Japan, n=50), South-East Africans (Mozambique, n=50), West-Africans (Ghana, n=50), and Indians (Argentina, n=50). We identified the most common FCN gene polymorphisms in five ethnic groups. Large ethnic differences were observed and the African populations contained several SNPs that were not observed in the other groups. Several variations, that will have major impact on the function of the ficolin proteins, were found. Three novel amino acid variations in Ficolin-1*Gly303Ser, Ficolin-2*Arg103Cys, and Ficolin-2*Thr137Met SNP were predicted by computational analyses to have a major functional physicochemical effect on their respective proteins. Additionally, a Gly43Asp in Ficolin-1 affects the Gly-Xaa-Yaa repeats and a Trp279STOP introduces a stop codon, thereby destroying the fibrinogen-like domain of Ficolin-1. In contrast to FCN1 and FCN2, the number of SNPs in FCN3 was very low. In conclusion, large ethnic differences in the FCN genes that will affect the concentration, structure, and function of the ficolin molecules were detected and which probably will be of pathophysiological relevance in different disease settings.
authors.affiliation: Department of Clinical Immunology, University of Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Hummelshøj
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000483:Alleles; D005006:Ethnicity / Q000235:genetics*; D005091:Exons; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D037102:Lectins / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000097604:Ficolins
chemical_list: D037102:Lectins; D000097604:Ficolins