title: A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative rheumatoid arthritis (RA) in a Danish population.
abstract: BACKGROUND
  It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case-control approach.
  
  
  RESULTS
  DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology.We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset.
  
  
  CONCLUSIONS
  These observations on a RA population of Danish ancestry suggest that variations in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including RA and SLE.
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholin Building 1240, Wilhelm Meyers Alle 4, 8000 Aarhus C, Denmark. laska@hum-gen.au.dk.
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Laska
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.forename: Anne
authors.initials: A
authors.lastname: Troldborg
authors.forename: Tove
authors.initials: T
authors.lastname: Lorenzen
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Lindegaard
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D003718:Denmark; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D051196:Toll-Like Receptor 3 / Q000235:genetics*
chemical_list: D051196:Toll-Like Receptor 3