TY - JOUR T1 - Association of <em>EMCN</em> with Susceptibility to Rheumatoid Arthritis in a Japanese Population JF - The Journal of Rheumatology JO - J Rheumatol SP - 221 LP - 228 DO - 10.3899/jrheum.100263 VL - 38 IS - 2 AU - KAZUMASA NISHIMOTO AU - KATSUNORI IKARI AU - HIROTAKA KANEKO AU - SO TSUKAHARA AU - YUTA KOCHI AU - KAZUHIKO YAMAMOTO AU - YUSUKE NAKAMURA AU - YOSHIAKI TOYAMA AU - ATSUO TANIGUCHI AU - HISASHI YAMANAKA AU - SHIGEKI MOMOHARA Y1 - 2011/02/01 UR - http://www.jrheum.org/content/38/2/221.abstract N2 - Objective. Endomucin, an endothelial-specific sialomucin, is thought to facilitate “lymphocyte homing” to synovial tissues, resulting in the major histopathologies of rheumatoid arthritis (RA). We examined the association between RA susceptibility and the gene coding endomucin, EMCN. Methods. Association studies were conducted with 2 DNA sample sets (initial set of 1504 patients, 752 controls; and validation set, 1113 patients, 940 controls) using 6 tag single-nucleotide polymorphisms (SNP) from the Japanese HapMap database. Immunohistochemistry for the expression of endomucin was conducted with synovial tissues from 4 patients with RA during total knee arthroplasty. Electromobility shift assays were performed for the functional study of identified polymorphisms. Results. Within the initial sample set, the strongest evidence of an association with RA susceptibility was SNP rs3775369 (OR 1.20, p = 0.0075). While the subsequent replication study did not initially confirm the observed significant association (OR 1.13, p = 0.062), an in-depth stratified analysis revealed significant association in patients testing positive to anti-cyclic citrullinated peptide (anti-CCP) antibody in the replication data set (OR 1.15, p = 0.044). Investigating 2 sample sets, significant associations were detected in overall and stratified samples with anti-CCP antibody status (OR 1.17, p = 0.0015). Positive staining for endomucin was detected in all patients. The allele associated with RA susceptibility had a higher binding affinity for HEK298-derived nuclear factors compared to the nonsusceptible allelic variant of rs3775369. Conclusion. A significant association between EMCN and RA susceptibility was detected in our Japanese study population. The EMCN allele conferring RA susceptibility may also contribute to the pathogenesis of RA. ER -