| Project/Area Number |
17K15631
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human genetics
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Research Collaborator |
Meguro Akira
Kastner Dan
Gül Ahmet
Mahmoudi Mahdi
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | ベーチェット病 / エピスタシス / MHCクラスI / ERAP1 / ERAP2 / SNP / HLAクラスI分子 / HLA-B*51 / HLA-A*26 / ゲノム / 遺伝子 / 遺伝子間相互作用 |
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| Outline of Final Research Achievements |
Behcet's disease is a systemic inflammatory disease clinically manifested as oral ulcers, uveitis, skin lesions and genital ulcers. Although disease pathogenesis remains unclear, it is thought that both multi genetic and environmental factors are associated with the onset of Behcet's disease. Recently, we reported that a single nucleotide polymorphism (SNP) in the locus of ERAP1, a gene of endoplasmic reticulum aminopeptidase, showed epistasis with the HLA-B*51 allele for the risk of Behcet's disease in the Turkish population. In this study, we conducted dense genotyping and imputation for the locus of ERAP1-ERAP2 and evaluated epistasis between HLA class I alleles and SNPs located in ERAP1-ERAP2. This study revealed the epistasis for the risk of Behcet's disease between HLA class I alleles such as HLA-B*51 and HLA-A*26, and SNPs in the locus of ERAP1-ERAP2.
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| Academic Significance and Societal Importance of the Research Achievements |
ベーチェット病の感受性遺伝子はこれまでに複数同定されているが、その発症メカニズムの全容解明には至っていない。本研究によりERAP1,ERAP2とMHCクラスI遺伝子の相互作用が示されたことで、ベーチェット病の病因となりうる特定のペプチドが存在する可能性とMHCクラスI分子が通した抗原提示が病態に深くかかわっていることが示唆された。本研究は、ベーチェット病の遺伝要因だけでなく病態理解にも大きく貢献するものである。
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