| Co-Investigator(Kenkyū-buntansha) |
MOCHIDA Satoshi Saitama Medical School, Medical, Professor, 医学部, 教授 (20219968)
ARAI Shin Saitama Medical School, Medical, Lecturer, 医学部, 講師 (20306294)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Osteopontin is an extra cellular matrix with RGD sequence, a cytokine essential for the initiation of Th1 immune reaction. We made transgenic mice expressing osteopontin exclusively in hepatocytes, and found that these mice had pathological characteristics similar to autoimmune hepatitis (AIH) in human, because antinuclear antibody was positive in the plasma, being accompanied by necrotic areas with lymphocyte infiltration in the liver. And, lymphocyte infiltration was recognized other internal organs of lung, salivary gland and digestive tract. Recently, we identified 4 SNPs (nt -155, -443, -616, -1,748) in the promoter region of human osteopontin gene, and demonstrated that SNP at nt -443 may be a useful marker to determine hepatitis activity in patients with chronic hepatitis C. Thus, it is suggested that SNPs in the promoter region of osteopontin gene may determine the development of ulcerative colitis and crohn's disease through regulation of osteopontin expression in the digestive tract, we evaluated this hypothesis by analysis of the SNPs in patients with ulcerative colitis and crohn's disease. The frequencies of alleles in SNP at nt -616 were 39% and 80% for G/G, 61% and 0% for G/T and 0% and 20% for T/T in patients with ulcerative colitis and crohn's disease. The frequencies of alleles in SNP at nt -443 were 6% and 20% for C/C, 55% and 40% for C/T and 39% and 40% for T/T in patients with ulcerative colitis and crohn's disease. G/G and G/T of alleles in SNP at nt -616 and T/T and C/T of alleles in SNP at nt -443 ware more get ill of ulcerative colitis and crohn's disease. The cases of serious illness used drugs of steroid and immune suppress were not different between alleles in SNP at nt -443 and nt -616. In the future, we will evaluate that it has more measure of osteopontin SNPs and explain the cause of serious illness.
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