title: The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study.
abstract: The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.
authors.affiliation: GenHotel-EA3886, Evry-Paris VII Universities, 91057 Evry-Genopole cedex, France. laurent@polyarthrite.net
authors.forename: Laurent
authors.initials: L
authors.lastname: Jacq
authors.forename: Sophie
authors.initials: S
authors.lastname: Garnier
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieudé
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Michou
authors.forename: Céline
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: Elodie
authors.initials: E
authors.lastname: Glikmans
authors.forename: Sandra
authors.initials: S
authors.lastname: Barbet
authors.forename: Sandra
authors.initials: S
authors.lastname: Lasbleiz
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lemaire
authors.forename: Patrick
authors.initials: P
authors.lastname: Quillet
authors.forename: Pascal
authors.initials: P
authors.lastname: Hilliquin
authors.forename: Vitor Hugo
authors.initials: VH
authors.lastname: Teixeira
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
authors.forename: Hamdi
authors.initials: H
authors.lastname: Mbarek
authors.forename: Bernard
authors.initials: B
authors.lastname: Prum
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: François
authors.initials: F
authors.lastname: Cornélis
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005060:Europe / Q000208:ethnology; D005192:Family Health / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D039564:Integrin alphaV