| Project/Area Number |
17390212
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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, Tohoku University, Department of internal medicine, Associate Professor (20250780)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Seiichi Tohoku University, Tohoku University hospital, Assistant Professor (40312574)
NEGORO Kenichi Tohoku University, Tohoku University hospital, Senior Residents (50375028)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,170,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2007: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2006: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | ulcerative colitis / susceptibility gene / HLA / IBD3 |
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| Research Abstract |
The human leukocyte antigen (HLA) region has been implicated in the pathogenesis of inflammatory bowel disease (IBD), which is classified into Cohn's disease (CD) and ulcerative colitis (UC). Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene was reported. BTNL2 is located in the HLA region and its messenger RNA is expressed most abundantly in the intestine. In this study, we performed a case-control association study of BTNL2 in the Japanese patients with IBD and performed linkage disequilibrium (LD) analysis between BTNL2 and HLA-DRB1. We analyzed eight polymorphisms selected after direct sequencing and found that none of the polymorphisms were associated with the Japanese CD cohort. In contrast, five polymorphisms were significantly associated with UC, especially three single nucleotide polymorphisms (BTNL2_19, BTNL2_22 and BTNL2_23) were associated as a haplotype. The most frequent haplotype (GGC haplotype) was a low-risk haplotype (P=0.000052), whereas the other TCT haplotype was a high-risk haplotype (P=0.0000085). Among the eight polymorphisms, the strongest association with UC was found in BTNL2_19 (OR=1.92, P=0.0000035). As expected, the BTNL2_19-T allele showed strong LD with DRB1*1502 (D'=0.92). When BTNL2_19 was tested as conditional on the DRB1*1502 carrier status, the significant association disappeared, suggesting that the association was because of its strong LD with DRB1*1502. We conclude that BTNL2 does not contribute to the susceptibility to Japanese CD but is associated with Japanese UC because of the strong LD with HLA-DRB1*1502. The strong LD between BTNL2 and HLA-DRB1 raises another issue about the potential role of BTNL2 in other diseases associated with HLA-DRB1.
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