Identification of genes regulating brain gray matter atrophy in Japanese multiple sclerosis by genome-wide association study

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21317
• Project/Area Number (Other): 18H06214 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyushu University
• Principal Investigator: Nakamura Yuri 九州大学, 医学研究院, 共同研究員 (40822375)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 多発性硬化症 / HLA / 頭部MRI / 脳萎縮

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.

Free Research Field

神経免疫

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。