Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the development of rheumatoid arthritis.
OBJECTIVE
We investigated the possible association of rheumatoid arthritis (RA) with single nucleotide polymorphisms (SNP) within the ficolin (FCN) genes. Two SNPs in the FCN1 gene, four SNPs in the FCN2 gene and one SNP in the FCN3 gene were studied.


METHODS
The SNPs within the FCN genes were detected by an experimental INNO-LiPA methodology (Innogenetics, Belgium) in a population consisting of 338 RA patients and 595 controls. The significant SNPs were further evaluated in two subpopulations and related to carriage of the human leukocyte antigen-shared epitope (HLA-SE), rheumatoid factor (RF) and the presence of anti-citrullinated protein/peptide antibodies (ACPA).


RESULTS
Two SNPs in the FCN1 gene were significantly associated with RA: the A allele rs2989727 was significantly increased in RA patients (67%) compared with controls (60%) (P = 0.002). Also, the frequency of the G allele of rs1071583 was increased in RA patients (68%) compared with controls (61%) (P = 0.003). Analysis of agreement between SNPs suggested strong linkage between rs2989727 and rs1071583. Carriage of a FCN1 SNP was independent of carriage of the HLA-SE, RF status and ACPA positivity.


CONCLUSIONS
We describe two linked SNPs in the FCN1 gene that are associated with the development of RA.
Vander Cruyssen
B
B
Department of Rheumatology, Ghent University Hospital, B-9000 Ghent, Belgium. Bert.VanderCruyssen@Ugent.be
Nuytinck
L
L
Boullart
L
L
Elewaut
D
D
Waegeman
W
W
Van Thielen
M
M
De Meester
E
E
Lebeer
K
K
Rossau
R
R
De Keyser
F
F
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D037102:Lectins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins