PT - JOURNAL ARTICLE AU - Jana Burkhardt AU - Elisabeth Petit-Teixeira AU - Vitor Hugo Teixeira AU - Holger Kirsten AU - Sophie Garnier AU - Sandra Ruehle AU - Christian Oeser AU - Grit Wolfram AU - Markus Scholz AU - Paola Migliorini AU - Alejandro Balsa AU - René Westhovens AU - Pilar Barrera AU - Helena Alves AU - Dora Pascual-Salcedo AU - Stefano Bombardieri AU - Jan Dequeker AU - Timothy R. Radstake AU - Piet Van Riel AU - Leo van de Putte AU - Thomas Bardin AU - Bernard Prum AU - Ulrike Buchegger-Podbielski AU - Frank Emmrich AU - Inga Melchers AU - François Cornelis AU - Peter Ahnert TI - Association of the X-Chromosomal Genes <em>TIMP1</em> and <em>IL9R</em> with Rheumatoid Arthritis AID - 10.3899/jrheum.090059 DP - 2009 Sep 01 TA - The Journal of Rheumatology PG - jrheum.090059 4099 - http://www.jrheum.org/content/early/2009/08/29/jrheum.090059.short 4100 - http://www.jrheum.org/content/early/2009/08/29/jrheum.090059.full AB - Objective Rheumatoid arthritis (RA) is an inflammatory joint disease with features of an autoimmune disease with female predominance. Candidate genes located on the X-chromosome were selected for a family trio-based association study. Methods A total of 1452 individuals belonging to 3 different sample sets were genotyped for 16 single-nucleotide polymorphisms (SNP) in 7 genes. The first 2 sets consisted of 100 family trios, each of French Caucasian origin, and the third of 284 additional family trios of European Caucasian origin. Subgroups were analyzed according to sex of patient and presence of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies. Results Four SNP were associated with RA in the first sample set and were genotyped in the second set. In combined analysis of sets 1 and 2, evidence remained for association of 3 SNP in the genes UBA1, TIMP1, and IL9R. These were again genotyped in the third sample set. Two SNP were associated with RA in the joint analysis of all samples: rs6520278 (TIMP1) was associated with RA in general (p = 0.035) and rs3093457 (IL9R) with anti-CCP-positive RA patients (p = 0.037) and male RA patients (p = 0.010). A comparison of the results with data from whole-genome association studies further supports an association of RA with TIMP1. The sex-specific association of rs3093457 (IL9R) was supported by the observation that men homozygous for rs3093457-CC are at a significantly higher risk to develop RA than women (risk ratio male/female = 2.98; p = 0.048). Conclusion We provide evidence for an association of at least 2 X-chromosomal genes with RA: TIMP1 (rs6520278) and IL9R (rs3093457).