PMID- 33898740
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231022
IS  - 2376-7839 (Print)
IS  - 2376-7839 (Electronic)
IS  - 2376-7839 (Linking)
VI  - 7
IP  - 2
DP  - 2021 Apr
TI  - Interactive Effects of HLA and GM Alleles on the Development of Alzheimer 
      Disease.
PG  - e565
LID - 10.1212/NXG.0000000000000565 [doi]
LID - e565
AB  - OBJECTIVE: We investigated whether particular immunoglobulin GM (gamma marker) 
      alleles-individually or epistatically with a known human leukocyte antigen (HLA) 
      risk allele-were associated with the development of Alzheimer disease (AD). 
      METHODS: Using a prospective cohort study design, we genotyped DNA samples from 
      209 African American (AA) and 638 European American (EA) participants for IgG1 
      (GM 3 and GM 17), IgG2 (GM 23+ and GM 23-), and HLA-DRB1 rs9271192 (A/C) alleles 
      by TaqMan and rhAMP genotyping assays. RESULTS: In EA subjects, none of the GM or 
      HLA alleles-individually or epistatically-were associated with time to 
      development of AD. In AA subjects, GM and HLA alleles individually were not 
      associated with time to development of AD. However, there was a significant 
      interaction: In the presence of GM 3 (i.e., GM 3/3 and GM 3/17 subjects), the 
      presence of the HLA-C allele was associated with a 4-fold increase in the 
      likelihood of developing AD compared with its absence (hazard ratio [HR] 4.17, 
      95% CI, 1.28-13.58). In the absence of GM 3 (GM 17/17 subjects), however, the 
      presence of the HLA-C allele was not associated with time to development of AD 
      (HR 1.10, 95% CI, 0.50-2.41). CONCLUSIONS: These results show that particular GM 
      and HLA alleles epistatically contribute to the development of AD.
CI  - Copyright (c) 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Pandey, Janardan P
AU  - Pandey JP
AUID- ORCID: 0000-0001-9992-4737
AD  - Department of Microbiology and Immunology (J.P.P., R.T.K.) and Department of 
      Public Health, Sciences (P.J.N.), Medical University of South Carolina, 
      Charleston; and Rush Alzheimer's Disease Center (L.L.B., D.A.B.), Rush University 
      Medical Center, Chicago, IL.
FAU - Nietert, Paul J
AU  - Nietert PJ
AD  - Department of Microbiology and Immunology (J.P.P., R.T.K.) and Department of 
      Public Health, Sciences (P.J.N.), Medical University of South Carolina, 
      Charleston; and Rush Alzheimer's Disease Center (L.L.B., D.A.B.), Rush University 
      Medical Center, Chicago, IL.
FAU - Kothera, Ronald T
AU  - Kothera RT
AD  - Department of Microbiology and Immunology (J.P.P., R.T.K.) and Department of 
      Public Health, Sciences (P.J.N.), Medical University of South Carolina, 
      Charleston; and Rush Alzheimer's Disease Center (L.L.B., D.A.B.), Rush University 
      Medical Center, Chicago, IL.
FAU - Barnes, Lisa L
AU  - Barnes LL
AD  - Department of Microbiology and Immunology (J.P.P., R.T.K.) and Department of 
      Public Health, Sciences (P.J.N.), Medical University of South Carolina, 
      Charleston; and Rush Alzheimer's Disease Center (L.L.B., D.A.B.), Rush University 
      Medical Center, Chicago, IL.
FAU - Bennett, David A
AU  - Bennett DA
AD  - Department of Microbiology and Immunology (J.P.P., R.T.K.) and Department of 
      Public Health, Sciences (P.J.N.), Medical University of South Carolina, 
      Charleston; and Rush Alzheimer's Disease Center (L.L.B., D.A.B.), Rush University 
      Medical Center, Chicago, IL.
LA  - eng
GR  - P30 AG010161/AG/NIA NIH HHS/United States
GR  - R01 AG015819/AG/NIA NIH HHS/United States
GR  - R01 AG022018/AG/NIA NIH HHS/United States
GR  - UL1 TR001450/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20210216
PL  - United States
TA  - Neurol Genet
JT  - Neurology. Genetics
JID - 101671068
PMC - PMC8063623
EDAT- 2021/04/27 06:00
MHDA- 2021/04/27 06:01
PMCR- 2021/02/16
CRDT- 2021/04/26 06:00
PHST- 2020/07/15 00:00 [received]
PHST- 2020/12/22 00:00 [accepted]
PHST- 2021/04/26 06:00 [entrez]
PHST- 2021/04/27 06:00 [pubmed]
PHST- 2021/04/27 06:01 [medline]
PHST- 2021/02/16 00:00 [pmc-release]
AID - NG2020015008 [pii]
AID - 10.1212/NXG.0000000000000565 [doi]
PST - epublish
SO  - Neurol Genet. 2021 Feb 16;7(2):e565. doi: 10.1212/NXG.0000000000000565. 
      eCollection 2021 Apr.