An identilication of the critical region for ulcerative colitis using the high resolution microsatellite mapping in IBD3
| Project/Area Number |
13470117
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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 | NIIGATA UNIVERSITY |
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Principal Investigator |
HONMA Terasu Niigata University, Graduate school of medical and dental sciences, Assistant, 大学院・医歯学総合研究科, 助手 (90272814)
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| Co-Investigator(Kenkyū-buntansha) |
ASAKURA Hitoshi Niigata University, Graduate school of medical and dental sciences, Professor, 大学院・医歯学総合研究科, 教授 (20051451)
INOKO Hidetoshi Toukai University, Faculty of Medicine, Professor, 医学部, 教授 (10101932)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥13,300,000 (Direct Cost: ¥13,300,000)
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| Keywords | Ulcerative colitis / Responsible gene / Chromosome 6 / IBD3 / Case-control study / Linkage disequilibrium / HLA抗原領域 / 複合遺伝性疾患 / 日本人 / ユダヤ人 / IkBL |
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| Research Abstract |
Background & Aims : As ulcerative colitis (UC) is the complex multifactorial traits involving both environmentaland genetic factors, the responsible loci for disease susceptibility is difficult to be determined. In Japanese patients with UC, we, have reported a conserved haplotype of HLA A24-B52-DR2(15)-DPw9 and a significantly high frequency of the MHC class I chain-related gene A (MICA) A6 allele. To precisely map the responsible gene involved in the development of UC, twenty-live markers distributed over a whole human MHC region were subjected to association analysis
Methods : Forty-nine patients with UC and 236 unrelated controls were included in this study. All subjects were Japanese. Twenty-two microsatellite markers, seven of which were found recently by our large genome sequencing, were determined by direct sequencing procedures HLA-A, B, and DR serotype were also decided. The significance of association was tested by thex^2 method. All P values were corrected by multiplication
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by the number of decided alleles of each locus (Pc). In addition, linkage disequilibria among associated markers were evaluated with t value
Results : One or more alleles showed significantly higherfrequencies in patients with UC at many loci, compared with controls. Two patients were homozygous for susceptible haplotype (B52-DR2(15)), and more detailed alleles about the susceptible haplotype were determined. Among these alleles, the maximum odds trio (OR) and lowest Pc value of phenotype frequency were observed at the marker of C1-2-A (allele 238), located approximately 147 kb centromeric to the HLA-B gene (OR=4.37, 95%CI 2.35-8.12, Pc=0.000042). No significant association was observed at the microsatellite markers distributed both centromeric to HLADP and telomeric to HLA-A locus. The highest t value was observed between C1-2-A (allele 238) and TNR-a (allele 119) (t value=14.62), and this region of susceptible haplotype were strongly conserved in Japanese patients with UC
Conclusions : These observations may indicate the existence of important determinants of disease susceptibility to UC between C1-2-A and TNF-a microsatellite markers on the short arm of chromosome 6. Interestingly, this conserved region does not contain the classical HLA locus. High resolution mapping. of responsible gene locus in this region will provide a new view on the pathogenesis of UC Less
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Report
(3 results)
Research Products
(1 results)
