PMID- 27056077
OWN - NLM
STAT- MEDLINE
DCOM- 20180309
LR  - 20181113
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 54
IP  - 5
DP  - 2017 Jul
TI  - Genetic Association of HLA Gene Variants with MRI Brain Structure in Alzheimer's 
      Disease.
PG  - 3195-3204
LID - 10.1007/s12035-016-9889-z [doi]
AB  - There is accumulating evidence that the human leukocyte antigen (HLA) gene 
      variants are associated with Alzheimer's disease (AD). However, how they affect 
      AD occurrence is still unknown. In this study, we firstly investigated the 
      association of gene variants in HLA gene variants and brain structures on MRI in 
      a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to 
      explore the effects of HLA on AD pathogenesis. We selected hippocampus, 
      hippocampus CA1 subregion, parahippocampus, posterior cingulate, precuneus, 
      middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). 
      According to the previous association studies of HLA variants and AD, 12 SNPs in 
      HLA were identified in the dataset following quality control measures. In total 
      group analysis, our results showed that TNF-alpha SNPs at rs2534672 and rs2395488 
      were significantly positively associated with the volume of the left middle 
      temporal lobe (rs2534672: P = 0.00035, Pc = 0.004; rs2395488: P = 0.0038, 
      Pc = 0.023) at baseline. In the longitudinal study, HFE rs1800562 was remarkably 
      correlated with the lower atrophy rate of right middle temporal lobe (P = 0.0003, 
      Pc = 0.003) and RAGE rs2070600 was associated with the atrophy rate of right 
      hippocampus substructure-CA1 over 2 years (P = 0.003, Pc = 0.035). Furthermore, 
      we detected the above four associations in mild cognitive impairment (MCI) 
      subgroup analysis, as well as the association of rs2534672 with the baseline 
      volume of the left middle temporal lobe in normal cognition (NC) subgroup 
      analysis. Our study provided preliminary evidences that HLA gene variants might 
      participate in the structural alteration of AD associated brain regions, hence 
      modulating the susceptibility of AD.
FAU - Wang, Zi-Xuan
AU  - Wang ZX
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
FAU - Wan, Yu
AU  - Wan Y
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
FAU - Tan, Lin
AU  - Tan L
AD  - College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 
      266000, China.
FAU - Liu, Jinyuan
AU  - Liu J
AD  - Columbia College, Columbia University, New York, NY, USA.
FAU - Wang, Hui-Fu
AU  - Wang HF
AD  - Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, 
      Qingdao, China.
FAU - Sun, Fu-Rong
AU  - Sun FR
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
FAU - Tan, Meng-Shan
AU  - Tan MS
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
FAU - Tan, Chen-Chen
AU  - Tan CC
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
FAU - Jiang, Teng
AU  - Jiang T
AD  - Department of Neurology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, China.
FAU - Tan, Lan
AU  - Tan L
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. 
      dr.tanlan@163.com.
AD  - College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 
      266000, China. dr.tanlan@163.com.
FAU - Yu, Jin-Tai
AU  - Yu JT
AD  - Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao 
      University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. 
      yu-jintai@163.com.
AD  - Memory and Aging Center, Department of Neurology, University of California, 675 
      Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA, 94158, USA. 
      yu-jintai@163.com.
CN  - Alzheimer's Disease Neuroimaging Initiative
LA  - eng
GR  - U01 AG024904/AG/NIA NIH HHS/United States
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160407
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*genetics/*pathology
MH  - Brain/*pathology
MH  - Female
MH  - *Genetic Association Studies
MH  - Genetic Loci
MH  - Genetic Predisposition to Disease
MH  - *Genetic Variation
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - *Magnetic Resonance Imaging
MH  - Male
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Brain structure
OT  - Genetics
OT  - HLA
OT  - Neuroimaging
EDAT- 2016/04/09 06:00
MHDA- 2018/03/10 06:00
CRDT- 2016/04/09 06:00
PHST- 2016/02/16 00:00 [received]
PHST- 2016/03/28 00:00 [accepted]
PHST- 2016/04/09 06:00 [pubmed]
PHST- 2018/03/10 06:00 [medline]
PHST- 2016/04/09 06:00 [entrez]
AID - 10.1007/s12035-016-9889-z [pii]
AID - 10.1007/s12035-016-9889-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2017 Jul;54(5):3195-3204. doi: 10.1007/s12035-016-9889-z. Epub 
      2016 Apr 7.