論文

査読有り 国際誌
2024年1月2日

The HLA-DRB1*09:01-DQB1*03:03 haplotype is associated with the risk for late-onset Alzheimer's disease in APOE [Formula: see text]4-negative Japanese adults.

npj aging
  • Daichi Shigemizu
  • Koya Fukunaga
  • Akiko Yamakawa
  • Mutsumi Suganuma
  • Kosuke Fujita
  • Tetsuaki Kimura
  • Ken Watanabe
  • Taisei Mushiroda
  • Takashi Sakurai
  • Shumpei Niida
  • Kouichi Ozaki
  • 全て表示

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開始ページ
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終了ページ
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記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41514-023-00131-3

Late-onset Alzheimer's disease (LOAD) is the most common cause of dementia among those older than 65 years. The onset of LOAD is influenced by neuroinflammation. The human leukocyte antigen (HLA) system is involved in regulating inflammatory responses. Numerous HLA alleles and their haplotypes have shown varying associations with LOAD in diverse populations, yet their impact on the Japanese population remains to be elucidated. Here, we conducted a comprehensive investigation into the associations between LOAD and HLA alleles within the Japanese population. Using whole-genome sequencing (WGS) data from 303 LOAD patients and 1717 cognitively normal (CN) controls, we identified four-digit HLA class I alleles (A, B, and C) and class II alleles (DRB1, DQB1, and DPB1). We found a significant association between the HLA-DRB1*09:01-DQB1*03:03 haplotype and LOAD risk in APOE [Formula: see text]4-negative samples (odds ratio = 1.81, 95% confidence interval = 1.38-2.38, P = 2.03[Formula: see text]). These alleles not only showed distinctive frequencies specific to East Asians but demonstrated a high degree of linkage disequilibrium in APOE [Formula: see text]4-negative samples (r2 = 0.88). Because HLA class II molecules interact with T-cell receptors (TCRs), we explored potential disparities in the diversities of TCR α chain (TRA) and β chain (TRB) repertoires between APOE [Formula: see text]4-negative LOAD and CN samples. Lower diversity of TRA repertoires was associated with LOAD in APOE [Formula: see text]4-negative samples, irrespective of the HLA DRB1*09:01-DQB1*03:03 haplotype. Our study enhances the understanding of the etiology of LOAD in the Japanese population and provides new insights into the underlying mechanisms of its pathogenesis.

リンク情報
DOI
https://doi.org/10.1038/s41514-023-00131-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/38167405
ID情報
  • DOI : 10.1038/s41514-023-00131-3
  • PubMed ID : 38167405

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