| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Outline of Final Research Achievements |
We collected DNA samples and clinical information from more than 400 patients with Takayasu arteritis (TAK). We identified a novel susceptibility HLA-B allele and two novel non-HLA susceptibility loci. The top SNP in the IL12B region showed high odds ratio and was associated with complication and severity of aortic regurgitation, a severe complication of TAK. Furthermore, the SNP demonstrated a synergistic effect with HLA-B*52:01, the strongest HLA susceptibility allele to TAK. These results indicate that IL12p40, encoded by IL12B, is a key molecule to TAK. Furthermore, we showed that 6.4% of patients with TAK suffered from ulcerative colitis (UC), one of inflammatory bowel diseases (IBD). We also showed a significant genetic overlap between TAK and UC, suggesting that the two diseases share common molecular pathways. Furthermore, we showed that ustekinumab, a monoclonal antibody to IL12p40 used for patients with IBD, was effective to patients with TAK in a pilot clinical study.
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