PMID- 38167405
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240105
IS  - 2731-6068 (Electronic)
IS  - 2731-6068 (Linking)
VI  - 10
IP  - 1
DP  - 2024 Jan 2
TI  - 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.
PG  - 3
LID - 10.1038/s41514-023-00131-3 [doi]
LID - 3
AB  - 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 (r(2) = 0.88). Because HLA class II molecules interact with T-cell 
      receptors (TCRs), we explored potential disparities in the diversities of TCR alpha 
      chain (TRA) and beta 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.
CI  - (c) 2024. The Author(s).
FAU - Shigemizu, Daichi
AU  - Shigemizu D
AUID- ORCID: 0000-0002-4412-0552
AD  - Medical Genome Center, Research Institute, National Center for Geriatrics and 
      Gerontology, Obu, Aichi, 474-8511, Japan. daichi@ncgg.go.jp.
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, 
      Japan. daichi@ncgg.go.jp.
AD  - Department of Cardiovascular Medicine, Hiroshima University Graduate School of 
      Biomedical and Health Sciences, Hiroshima, 734-8551, Japan. daichi@ncgg.go.jp.
FAU - Fukunaga, Koya
AU  - Fukunaga K
AUID- ORCID: 0000-0002-5241-6062
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, 
      Japan.
FAU - Yamakawa, Akiko
AU  - Yamakawa A
AUID- ORCID: 0009-0003-2255-4418
AD  - Medical Genome Center, Research Institute, National Center for Geriatrics and 
      Gerontology, Obu, Aichi, 474-8511, Japan.
FAU - Suganuma, Mutsumi
AU  - Suganuma M
AD  - Medical Genome Center, Research Institute, National Center for Geriatrics and 
      Gerontology, Obu, Aichi, 474-8511, Japan.
FAU - Fujita, Kosuke
AU  - Fujita K
AD  - Department of Prevention and Care Science, Research Institute, National Center 
      for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.
AD  - Japan Society for the Promotion of Science, Tokyo, 102-0083, Japan.
FAU - Kimura, Tetsuaki
AU  - Kimura T
AUID- ORCID: 0000-0002-2010-104X
AD  - Medical Genome Center, Research Institute, National Center for Geriatrics and 
      Gerontology, Obu, Aichi, 474-8511, Japan.
FAU - Watanabe, Ken
AU  - Watanabe K
AD  - NCGG Biobank, National Center for Geriatrics and Gerontology, Obu, Aichi, 
      474-8511, Japan.
FAU - Mushiroda, Taisei
AU  - Mushiroda T
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, 
      Japan.
FAU - Sakurai, Takashi
AU  - Sakurai T
AD  - Department of Prevention and Care Science, Research Institute, National Center 
      for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.
FAU - Niida, Shumpei
AU  - Niida S
AD  - Core Facility Administration, Research Institute, National Center for Geriatrics 
      and Gerontology, Aichi, 474-8511, Japan.
FAU - Ozaki, Kouichi
AU  - Ozaki K
AUID- ORCID: 0000-0003-0028-1570
AD  - Medical Genome Center, Research Institute, National Center for Geriatrics and 
      Gerontology, Obu, Aichi, 474-8511, Japan. ozakikk@ncgg.go.jp.
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, 
      Japan. ozakikk@ncgg.go.jp.
AD  - Department of Cardiovascular Medicine, Hiroshima University Graduate School of 
      Biomedical and Health Sciences, Hiroshima, 734-8551, Japan. ozakikk@ncgg.go.jp.
LA  - eng
GR  - JP21H02470/MEXT | Japan Society for the Promotion of Science (JSPS)/
GR  - JP21de0107002/Japan Agency for Medical Research and Development (AMED)/
GR  - JP21dk0207052/Japan Agency for Medical Research and Development (AMED)/
GR  - JP21dk0207045/Japan Agency for Medical Research and Development (AMED)/
GR  - JP22dk0207060/Japan Agency for Medical Research and Development (AMED)/
GR  - JP21de0107002/Japan Agency for Medical Research and Development (AMED)/
GR  - JP21dk0207052/Japan Agency for Medical Research and Development (AMED)/
GR  - JP18kk0205009/Japan Agency for Medical Research and Development (AMED)/
GR  - JP18kk0205012/Japan Agency for Medical Research and Development (AMED)/
GR  - JP21km0405501/Japan Agency for Medical Research and Development (AMED)/
GR  - JP21dk0207045/Japan Agency for Medical Research and Development (AMED)/
GR  - JP22dk0207060/Japan Agency for Medical Research and Development (AMED)/
PT  - Journal Article
DEP - 20240102
PL  - England
TA  - NPJ Aging
JT  - npj aging
JID - 9918402285106676
PMC - PMC10761915
COIS- The authors declare no competing interests.
EDAT- 2024/01/04 01:18
MHDA- 2024/01/04 01:19
PMCR- 2024/01/02
CRDT- 2024/01/03 09:48
PHST- 2023/09/27 00:00 [received]
PHST- 2023/11/22 00:00 [accepted]
PHST- 2024/01/04 01:19 [medline]
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/03 09:48 [entrez]
PHST- 2024/01/02 00:00 [pmc-release]
AID - 10.1038/s41514-023-00131-3 [pii]
AID - 131 [pii]
AID - 10.1038/s41514-023-00131-3 [doi]
PST - epublish
SO  - NPJ Aging. 2024 Jan 2;10(1):3. doi: 10.1038/s41514-023-00131-3.