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AB0154 The il12rb2 gene is a novel candidate susceptible to systemic sclerosis in the japanese population
  1. Y. Ota1,
  2. Y. Kawaguchi1,
  3. T. Nishimoto2,
  4. M. Kuwana2,
  5. H. Ichida1,
  6. T. Gono1,
  7. H. Yamanaka1
  1. 1Institute of Rheumatology, Tokyo Women’s Medical University
  2. 2Division of Rheumatology, Keio University School of Medicine, Tokyo, Japan


Background Systemic sclerosis (SSc) is a multisystem disorder of connective tissue characterized by excessive accumulation of extracellular matrix in the skin and various internal organs. Some clinical studies have shown that autoantibodies and genetic polymorphisms could reflect clinical manifestations of SSc. IL12RB2 genetic variants have been associated with multiple autoimmune disorders. In 2012, Bossini-Castillo et al. revealed the association of an IL12RB2 genetic variant with SSc in Caucasian populations.

Objectives In this study we explored the association of a single nucleotide polymorphism (SNP) of the IL12RB2 gene with susceptibility to SSc in the Japanese population.

Methods Four hundred thirty-five patients with SSc, 46 patients with SLE and 322 healthy controls (HC) were enrolled in this study. Three SNPs (rs1495965, rs924080, and rs3790567) in the IL12RB2 gene were determined by allelic discrimination with the use of each specific TaqMan probe. In patients with SSc, the number of female and male was three hundred eighty-nine and forty-six. The frequencies of the patients with diffuse cutaneous type were 47%, interstitial lung disease were 55%, and anti-topoisomerase I positivity were 33%.

Results Only a SNP (rs1495965) was significantly associated with susceptibility to SSc in the Japanese population. At rs1495965, the C allele showed a significantly higher frequency in patients with SScthan that in controls (P = 0.0060; odds ratio, 1.34; 95% confidence interval, 1.1-1.7). In this study, we didn’t support an association of IL12RB2 rs924080 and rs3790567 with SSc, as previously reported in Caucasian populations. In contrast, any significant associations of SLE with the SNPs were observed in the present study. In particular, the clinical subsets of SSc showed a more significant association between the C allele and diffuse cutaneous SSc (dcSSc, P = 0.0015) and the presence of interstitial lung disease (ILD, P = 0.0022), the presence of anti-topoisomerase antibody (Topo, P = 0.00039). We showed the significant association between a SNP in the IL12RB2 gene and susceptibility to SSc in the Japanese population, especially in the presence of dcSSc, ILD, and Topo. However, the SNP we found as a susceptibility gene in the present study was different from the SNP previously reported in the Caucasian population.

Conclusions The IL12RB2 gene was one of susceptibility-genes in patients with SSc. Our results strongly suggest that this SNP may be a powerful indicator for the severity of skin and lung involvement in patients with SSc.

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  2. Dieude P, Guedj M, Wipff J, et al. Association between the IRF5 re2004640 functional polymorphism and systemic sclerosis: a new perspective for pulmonary fibrosis. Arthritis Rheum 2009;60:225-33

  3. Mizuki N, Meguro A, Ota M, et al. Genome-wide association studies identify IL23R-IL12RB2 and IL-10 as Behcet’s disease susceptibility loci. Nat Genet 2010; 42:703-706

  4. Bossini-Castillo L, Martin JE, Broen J, et al. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations. Hum Mol Genet 2012;21:926-933

Disclosure of Interest None Declared

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