Identification of genes regulating brain gray matter atrophy in Japanese multiple sclerosis by genome-wide association study
Project/Area Number |
19K21317
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Project/Area Number (Other) |
18H06214 (2018)
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund (2019) Single-year Grants (2018) |
Review Section |
0902:General internal medicine and related fields
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Research Institution | Kyushu University |
Principal Investigator |
Nakamura Yuri 九州大学, 医学研究院, 共同研究員 (40822375)
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Project Period (FY) |
2018-08-24 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 多発性硬化症 / HLA / 頭部MRI / 脳萎縮 / 全ゲノム関連解析 |
Outline of Research at the Start |
多発性硬化症(MS)の疾患修飾薬は、慢性的な障害進行には無効で最大のアンメットニーズとなっている。MSの障害進行は脳萎縮と最も強く相関するが、私達は、多数例の日本人と欧米人のMS のMRI 画像の比較により、両者とも大脳皮質容積と深部灰白質容積が障害の進行と強く相関することを見出した。しかも深部灰白質の萎縮速度は日本人MS が欧米人MS より有意に速かった。しかし、このようなMS の脳萎縮を規定する遺伝的要因は不明である。そこで、本研究では大脳各部位、特に障害進行に密接に関わる灰白質容積の減少と有意に相関するリスク遺伝子・保護的遺伝子を全ゲノム関連解析(GWAS)により同定する。
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Outline of Final Research Achievements |
A total of 66 patients with multiple sclerosis (MS) underwent brain MRI volumetry measuring and HLA-DRB1 genotyping. HLA-based differences in MRI parameters including brain volume loss and accumulation of lesion load were assessed. HLA-DRB1*15:01 carriers had a significantly faster reduction in normalized whole-brain white matter volumes than DRB1*15:01 non-carriers, whereas HLA-DRB1*04:05 carriers had a significantly slower increase in lesion volumes than HLA-DRB1*04:05 non-carriers. Our study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS. We will conduct genome-wide association study to find additional genes regulating brain atrophy and accumulation of lesion load in a larger cohort.
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Academic Significance and Societal Importance of the Research Achievements |
MSの脳萎縮は非可逆的な神経軸索変性を反映し、MSの慢性障害進行を予測するバイオマーカーとして注目されている。脳萎縮は進行期に特徴的な所見ではなく、病初期から認められることから、脳萎縮をいかに早期から予防するかがMSの慢性的な障害進行を食い止める上で極めて重要である。今回、日本人MSにおける脳萎縮並びに病巣蓄積と関連するHLA遺伝子を明らかにした。脳萎縮の機序の解明、ひいては治療標的の同定に寄与するもとと考えられる。
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Report
(3 results)
Research Products
(6 results)
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[Journal Article] Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis2020
Author(s)
Fukumoto S, Nakamura Y, Watanabe M, Isobe N, Matsushita T, Sakoda A, Hiwatashi A, Shinoda K, Yamasaki R, Tsujino A, Kira J.
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Journal Title
Journal of the Neurological Sciences
Volume: 413
Pages: 116768-116768
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Spinal cord involvement by atrophy and associations with disability are different between multiple sclerosis and neuromyelitis optica spectrum disorder2019
Author(s)
Nakamura Y, Liu Z, Fukumoto S, Shinoda K, Sakoda A, Matsushita T, Hayashida S, Isobe N, Watanabe M, Hiwatashi A, Yamasaki R, Kira J.
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Journal Title
European Journal of Neurology
Volume: 27
Issue: 1
Pages: 92-99
DOI
Related Report
Peer Reviewed / Open Access
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