title: Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedic Surgery, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 162-8582, Japan. knishimoto@a2.keio.jp
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Nishimoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kaneko
authors.forename: So
authors.initials: S
authors.lastname: Tsukahara
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Atsuo
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012795:Sialoglycoproteins / Q000235:genetics*
chemical_list: C431275:EMCN protein, human; D012795:Sialoglycoproteins