Abstract | OBJECTIVE: 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.
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Authors | Kazumasa Nishimoto, Katsunori Ikari, Hirotaka Kaneko, So Tsukahara, Yuta Kochi, Kazuhiko Yamamoto, Yusuke Nakamura, Yoshiaki Toyama, Atsuo Taniguchi, Hisashi Yamanaka, Shigeki Momohara |
Journal | The Journal of rheumatology
(J Rheumatol)
Vol. 38
Issue 2
Pg. 221-8
(Feb 2011)
ISSN: 0315-162X [Print] Canada |
PMID | 21159824
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- EMCN protein, human
- Sialoglycoproteins
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Topics |
- Adult
- Alleles
- Arthritis, Rheumatoid
(genetics)
- Asian People
(genetics)
- Electrophoretic Mobility Shift Assay
- Enzyme-Linked Immunosorbent Assay
- Female
- Gene Frequency
- Genetic Association Studies
- Genetic Predisposition to Disease
- Genotype
- Haplotypes
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Odds Ratio
- Polymorphism, Single Nucleotide
- Sialoglycoproteins
(genetics)
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