2003 Fiscal Year Final Research Report Summary
Analysis of susceptibility gene to Crohn's disease in the HLA region
| Project/Area Number |
13470110
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
KINOUCHI Yoshitaka Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20250780)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Seiichi Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (40312574)
UENO Yoshiyuki Tohoku University, Hospital, Lecture, 医学部附属病院, 講師 (70282126)
SHIMOSEGAWA Tooru Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90226275)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Crohn's disease / Susceptibility gene / polymorphism / association study / HLA / TNF-α |
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| Research Abstract |
Though etiology of Crohn's disease and ulcerative colitis still remains unclear, a lot of studies have shown that genetic background is important in susceptibility to Crohn's disease and ulcerative colitis. To identify the susceptibility genes to Crohn's disease and ulcerative colitis, we have performed association mapping in the chromosome 6p. In Crohn's disease, we have determined two independent association peaks, one is near the HLA-DQB1 gene, the other is near the TNF gene. Concerning ulcerative colitis, association mapping has demonstrated that important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B^*52. According to our genetic analysis of the HLA region, the most attractive candidate gene was the TNF gene. I have already reported that SNPs in the 5'-flanking region are associated Crohn's disease. To determine functional significance, promoter analysis of the 5'-flanking region in the TNF gene was performed. The results of the promoter assay were not reproducible. The activity was revealed to depend on cells used in the assay.
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