The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study

Laurent Jacq¹^,2 , Sophie Garnier¹ , Philippe Dieudé¹^,3 , Laëtitia Michou¹^,4 , Céline Pierlot¹ , Paola Migliorini⁵ , Alejandro Balsa⁶ , René Westhovens⁷ , Pilar Barrera⁸ , Helena Alves⁹ , Carlos Vaz⁹ , Manuela Fernandes⁹ , Dora Pascual-Salcedo⁶ , Stefano Bombardieri⁵ , Jan Dequeker⁷ , Timothy R Radstake⁸ , Piet Van Riel⁸ , Leo van de Putte⁸ , Antonio Lopes-Vaz⁹ , Elodie Glikmans¹ , Sandra Barbet¹ , Sandra Lasbleiz¹^,4 , Isabelle Lemaire¹^,2 , Patrick Quillet¹^,2 , Pascal Hilliquin¹^,2 , Vitor Hugo Teixeira¹^,10 , Elisabeth Petit-Teixeira¹ , Hamdi Mbarek¹ , Bernard Prum¹¹ , Thomas Bardin¹^,4 and François Cornélis¹^,2^,12 for the European Consortium on Rheumatoid Arthritis Families

¹GenHotel-EA3886, Evry-Paris VII Universities, Member of the AutoCure European Consortium, 2 rue Gaston Crémieux, 91057 Evry-Genopole cedex, France

²Centre Hospitalier Sud Francilien, 59 bd Henri Dunant, 91100 Corbeil-Essonnes, France

³Service de rhumatologie, Hôpital Bichat, AP-HP, 46 rue Henri Huchart, 75018 Paris, France

⁴Service de rhumatologie, Hôpital Lariboisière, AP-HP, 2 rue Ambroise Paré, 75010 Paris, France

⁵Pisa University, 56126 Pisa, Italy

⁶La Paz Hospital, 28046 Madrid, Spain

⁷Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium

⁸Nijmegen University, 6500HB Nijmegen, The Netherlands

⁹Porto San Joao Hospital, 4200 Porto, Portugal

¹⁰Faculty of Medicine, University of Coimbra, Coimbra, Portugal

¹¹Laboratoire Statistique et Génome, Genopole, Tour Evry 2, 91000 Evry, France

¹²Unité de Génétique Clinique, Hôpital Lariboisière, AP-HP, 2 rue Ambroise Paré, 75010 Paris, France

author email corresponding author email

Arthritis Research & Therapy 2007, 9:R63doi:10.1186/ar2221


Published:	3 July 2007

See related editorial by Ahnert and Kirsten, http://arthritis-research.com/content/9/5/108 and related letter by Iikuni et al., http://arthritis-research.com/content/9/5/405

Abstract

The integrin αvβ3, whose αv 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% versus50% 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.