title: Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study.
abstract: BACKGROUND
  A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach.
  
  
  METHODS
  A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk.
  
  
  RESULTS
  We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients.
  
  
  CONCLUSIONS
  Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association.
authors.affiliation: GenHotel-EA3886, Evry University - Paris 7 University Medical School, AutoCure European Consortium, Evry-Genopole, France. vitor@polyarthrite.net
authors.forename: Vitor Hugo
authors.initials: VH
authors.lastname: Teixeira
authors.forename: Celine
authors.initials: C
authors.lastname: Pierlot
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: René
authors.initials: R
authors.lastname: Westhovens
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Helena
authors.initials: H
authors.lastname: Alves
authors.forename: Carlos
authors.initials: C
authors.lastname: Vaz
authors.forename: Manuela
authors.initials: M
authors.lastname: Fernandes
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Jan
authors.initials: J
authors.lastname: Dequeker
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Radstake
authors.forename: Piet
authors.initials: P
authors.lastname: Van Riel
authors.forename: Leo
authors.initials: L
authors.lastname: van de Putte
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopes-Vaz
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: Bernard
authors.initials: B
authors.lastname: Prum
authors.forename: François
authors.initials: F
authors.lastname: Cornélis
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005060:Europe; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000098546:Interleukin-21
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21