Systemic Sclerosis

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Association of a functional polymorphism in the IRF5 region with systemic sclerosis in a Japanese population

  1. Ikue Ito1,
  2. Yasushi Kawaguchi2,
  3. Aya Kawasaki1,
  4. Minoru Hasegawa3,
  5. Jun Ohashi1,
  6. Koki Hikami1,
  7. Manabu Kawamoto2,
  8. Manabu Fujimoto3,
  9. Kazuhiko Takehara3,†,
  10. Shinichi Sato4,
  11. Masako Hara2,
  12. Naoyuki Tsuchiya1,*

Article first published online: 28 MAY 2009

DOI: 10.1002/art.24600

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 60, Issue 6, pages 1845–1850, June 2009

Additional Information

How to Cite

Ito, I., Kawaguchi, Y., Kawasaki, A., Hasegawa, M., Ohashi, J., Hikami, K., Kawamoto, M., Fujimoto, M., Takehara, K., Sato, S., Hara, M. and Tsuchiya, N. (2009), Association of a functional polymorphism in the IRF5 region with systemic sclerosis in a Japanese population. Arthritis & Rheumatism, 60: 1845–1850. doi: 10.1002/art.24600

Author Information

  1. 1

    University of Tsukuba, Tsukuba, Japan

  2. 2

    Tokyo Women's Medical University, Tokyo, Japan

  3. 3

    Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

  4. 4

    Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

  1. †

    Dr. Takehara has received consulting fees from Benesis Corporation (more than $10,000).

*Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

Publication History

  1. Issue published online: 28 MAY 2009
  2. Article first published online: 28 MAY 2009
  3. Manuscript Accepted: 18 MAR 2009
  4. Manuscript Received: 17 SEP 2008

Funded by

  • Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science, Health, and Labour Sciences Research grants from the Ministry of Health, Labour, and Welfare of Japan
  • Japan Rheumatism Foundation
  • Naito Foundation
  • Mitsubishi Pharma Research Foundation

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Abstract

Objective

Interferon regulatory factor 5, an established susceptibility factor for systemic lupus erythematosus (SLE), plays a role in type I interferon and proinflammatory cytokine induction. A recent study showed association of a functional single-nucleotide polymorphism (SNP) in intron 1 of IRF5, rs2004640, with systemic sclerosis (SSc) in a European French population. We undertook the present study to determine whether IRF5 polymorphisms are also associated with a predisposition to SSc in Japanese.

Methods

A case–control association study was performed for rs2004640 as well as for rs10954213 and rs2280714, all of which were previously reported to be associated with SLE, in 281 SSc patients and 477 healthy controls. Patients with SSc complicated by SLE or Sjögren's syndrome were excluded. Association of the rs2280714 genotype with messenger RNA (mRNA) levels of IRF5 and adjacently located transportin 3 (TNPO3) was examined using the GENEVAR database.

Results

All 3 SNPs were significantly associated with SSc, with the rs2280714 A allele having the strongest association (allele frequency P = 0.0012, odds ratio 1.42 [95% confidence interval 1.15–1.75]). Association was preferentially observed in subsets of patients with diffuse cutaneous SSc (dcSSc) and anti–topoisomerase I antibody positivity. Conditional analysis revealed that rs2280714 could account for most of the association of these SNPs, while an additional contribution of rs2004640 was also suggested for dcSSc. The genotype of rs2280714 was strongly associated with IRF5 mRNA expression, while only marginal association was detected with TNPO3 mRNA expression.

Conclusion

Association of IRF5 with SSc was replicated in a Japanese population. Whether the causal SNP is different among populations requires further investigation.

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