Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population

Kazumasa Nishimoto, Katsunori Ikari, Hirotaka Kaneko, So Tsukahara, Yuta Kochi, Kazuhiko Yamamoto, Yusuke Nakamura, Yoshiaki Toyama, Atsuo Taniguchi, Hisashi Yamanaka, Shigeki Momohara

Research output: Contribution to journalArticle

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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. 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. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalJournal of Rheumatology
Volume38
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

Fingerprint

Sialomucins
Rheumatoid Arthritis
Population
Single Nucleotide Polymorphism
Alleles
HapMap Project
Knee Replacement Arthroplasties
Antibodies
Rheumatology
Immunohistochemistry
Databases
Lymphocytes
Staining and Labeling
DNA
Genes

Keywords

  • Endomucin
  • Gene
  • Rheumatoid arthritis
  • Susceptibility

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Nishimoto, K., Ikari, K., Kaneko, H., Tsukahara, S., Kochi, Y., Yamamoto, K., ... Momohara, S. (2011). Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population. Journal of Rheumatology, 38(2), 221-228. https://doi.org/10.3899/jrheum.100263

Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population. / Nishimoto, Kazumasa; Ikari, Katsunori; Kaneko, Hirotaka; Tsukahara, So; Kochi, Yuta; Yamamoto, Kazuhiko; Nakamura, Yusuke; Toyama, Yoshiaki; Taniguchi, Atsuo; Yamanaka, Hisashi; Momohara, Shigeki.

In: Journal of Rheumatology, Vol. 38, No. 2, 01.02.2011, p. 221-228.

Research output: Contribution to journalArticle

Nishimoto, K, Ikari, K, Kaneko, H, Tsukahara, S, Kochi, Y, Yamamoto, K, Nakamura, Y, Toyama, Y, Taniguchi, A, Yamanaka, H & Momohara, S 2011, 'Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population', Journal of Rheumatology, vol. 38, no. 2, pp. 221-228. https://doi.org/10.3899/jrheum.100263
Nishimoto K, Ikari K, Kaneko H, Tsukahara S, Kochi Y, Yamamoto K et al. Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population. Journal of Rheumatology. 2011 Feb 1;38(2):221-228. https://doi.org/10.3899/jrheum.100263
Nishimoto, Kazumasa ; Ikari, Katsunori ; Kaneko, Hirotaka ; Tsukahara, So ; Kochi, Yuta ; Yamamoto, Kazuhiko ; Nakamura, Yusuke ; Toyama, Yoshiaki ; Taniguchi, Atsuo ; Yamanaka, Hisashi ; Momohara, Shigeki. / Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population. In: Journal of Rheumatology. 2011 ; Vol. 38, No. 2. pp. 221-228.
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AU - Yamamoto, Kazuhiko

AU - Nakamura, Yusuke

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