RT Journal Article
SR Electronic
T1 Association of the X-Chromosomal Genes TIMP1 and IL9R with Rheumatoid Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 2149
OP 2157
DO 10.3899/jrheum.090059
VO 36
IS 10
A1 JANA BURKHARDT
A1 ELISABETH PETIT-TEIXEIRA
A1 VITOR HUGO TEIXEIRA
A1 HOLGER KIRSTEN
A1 SOPHIE GARNIER
A1 SANDRA RUEHLE
A1 CHRISTIAN OESER
A1 GRIT WOLFRAM
A1 MARKUS SCHOLZ
A1 PAOLA MIGLIORINI
A1 ALEJANDRO BALSA
A1 RENÈ WESTHOVENS
A1 PILAR BARRERA
A1 HELENA ALVES
A1 DORA PASCUAL-SALCEDO
A1 STEFANO BOMBARDIERI
A1 JAN DEQUEKER
A1 TIMOTHY R. RADSTAKE
A1 PIET Van RIEL
A1 LEO van de PUTTE
A1 THOMAS BARDIN
A1 BERNARD PRUM
A1 ULRIKE BUCHEGGER-PODBIELSKI
A1 FRANK EMMRICH
A1 INGA MELCHERS
A1 FRANÇOIS CORNELIS
A1 PETER AHNERT
YR 2009
UL http://www.jrheum.org/content/36/10/2149.abstract
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 TIMPL 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).