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Cited by 43Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

Association of HLA-DRB1 polymorphism with Alzheimer's disease: a replication and meta-analysis

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Lu, Rui-Chun, Yang, Wu, Tan, Lin, Sun, Fu-Rong, Tan, Meng-Shan, Zhang, Wei, Wang, Hui-Fu, Tan, Lan·2017·Oncotarget
DOI 10.18632/oncotarget.21479PMC PMC5696257
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Abstract

// Rui-Chun Lu 1 , Wu Yang 2 , Lin Tan 1 , Fu-Rong Sun 1 , Meng-Shan Tan 1 , Wei Zhang 1 , Hui-Fu Wang 1 and Lan Tan 1 1 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China 2 International Department, The Affiliated Hospital of Qingdao University, Qingdao, China Correspondence to: Lan Tan, email: dr.tanlan@163.com Keywords: Alzheimer’s disease, polymorphism, association study, HLA-DRB1, meta-analyses Received: April 19, 2017 Accepted: September 20, 2017 Published: October 04, 2017 ABSTRACT Genome-wide association studies (GWAS) have identified one single-nucleotide polymorphism (SNP) rs9271192 within HLA-DRB1 as a risk factor for Alzheimer's disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified in other ethnic cohorts. In order to evaluate the association between HLA-DRB1 rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD (genotype P = 0.015, allele P = 0.04). The results of logistic regression revealed the C allele homozygosity strongly increased the risk of LOAD under a recessive model in the total sample ( P = 0.004, OR =2.069, 95% CI = 1.262–3.434). When these data were stratified by apolipoprotein E ( APOE ) ε4 status, the observed association was confined to APOE ε4 non-carriers (additive model: P=0.048, OR =1.191, 95% CI =1.001–1.417; recessive model: P < 0.001, OR = 2.601, 95% CI =1.519–4.566). Furthermore, meta-analysis after sensitive analysis confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD (OR = 1.12, 95% CI = 1.08–1.15). To summarize, the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD.

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  • HLA-DRB polymorphisms are associated with increased risk of AD.

    “Moreover, HLA‐DRB polymorphisms are associated with increased risk of AD 2 , 19 , 20”

    From The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model (2022) · cites this paper as [19]

    The Discussion reports that the C allele of HLA-DRB1 rs9271192 is associated with increased risk of late-onset AD in a Northern Han Chinese population; the Abstract also reports a supporting meta-analysis. The cited paper supports that specific variant and disease subtype, not the broader claim about HLA-DRB polymorphisms generally. Page numbers are not provided in our copy. (LLM, conf=0.85)

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  1. [1]Guerini FR Tinelli C Calabrese E Agliardi C Zanzottera M De Silvestri A Franceschi M Grimaldi LM Nemni R Clerici M HLA-A*01 is associated with late onset of Alzheimer's disease in Italian patients Int J Immunopathol Pharmacol 2009 22 991 999 20074462
  2. [2]Cifuentes RA Murillo-Rojas J Alzheimer's disease and HLA-A2: linking neurodegenerative to immune processes through an in silico approach Biomed Res Int 2014 2014 791238 25197660 PMC4150521
  3. [4]Gatz M Reynolds CA Fratiglioni L Johansson B Mortimer JA Berg S Fiske A Pedersen NL Role of genes and environments for explaining Alzheimer disease Arch Gen Psychiat 2006 63 168 174 16461860
  4. [5]Hauser PS Ryan RO Impact of apolipoprotein E on Alzheimer's disease Curr Alzheimer Res 2013 10 809 817 23919769 PMC3995977
  5. [6]Jiang T Yu JT Wang YL Wang HF Zhang W Hu N Tan L Sun L Tan MS Zhu XC Tan L The genetic variation of ARRB2 is associated with late-onset Alzheimer's disease in Han Chinese Curr Alzheimer Res 2014 11 408 412 24635845
  6. [7]Xia M Yu JT Miao D Lu RC Zheng XP Tan L SIRT2 polymorphism rs10410544 is associated with Alzheimer's disease in a Han Chinese population J Neurol Sci 2014 336 48 51 24139700
  7. [9]Hollingworth P Harold D Sims R Gerrish A Lambert JC Carrasquillo MM Abraham R Hamshere ML Pahwa JS Moskvina V Dowzell K Jones N Stretton A Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease Nat Genet 2011 43 429 435 21460840 PMC3084173
  8. [10]Lambert JC Ibrahim-Verbaas CA Harold D Naj AC Sims R Bellenguez C DeStafano AL Bis JC Beecham GW Grenier-Boley B Russo G Thorton-Wells TA Jones N Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease Nat Genet 2013 45 1452 1458 24162737 PMC3896259
  9. [11]Yu JT Song JH Ma T Zhang W Yu NN Xuan SY Tan L Genetic association of PICALM polymorphisms with Alzheimer's disease in Han Chinese J Neurol Sci 2011 300 78 80 20951388
  10. [12]Yu JT Miao D Cui WZ Ou JR Tian Y Wu ZC Zhang W Tan L Common variants in toll-like receptor 4 confer susceptibility to Alzheimer's disease in a Han Chinese population Curr Alzheimer Res 2012 9 458 466 22272615
  11. [13]Wang W Yu JT Zhang W Cui WZ Wu ZC Zhang Q Tan L Genetic association of SLC2A14 polymorphism with Alzheimer's disease in a Han Chinese population J Mol Neurosci 2012 47 481 484 22421804
  12. [14]Wang HF Tan L Yu JT Ma XY Liu QY Wang W Age-dependent association of KIBRA gene polymorphism with Alzheimer's disease in Han Chinese Mol Biol Rep 2013 40 7077 7082 24190487
  13. [15]Zhang J Li Y SLC26A4 gene polymorphism and late-onset Alzheimer's disease in a Han Chinese population from Qingdao, China Neural Regen Res 2013 8 754 759 25206722 PMC4146073
  14. [16]Xiao Q Liu ZJ Tao S Sun YM Jiang D Li HL Chen H Liu X Lapin B Wang CH Zheng SL Xu J Wu ZY Risk prediction for sporadic Alzheimer's disease using genetic risk score in the Han Chinese population Oncotarget 2015 6 36955 36964 http://doi.org/10.18632/oncotarget.6271 26543236 PMC4741908 · DOI
  15. [17]Jiao B Liu X Zhou L Wang MH Zhou Y Xiao T Zhang W Sun R Waye MM Tang B Shen L Polygenic Analysis of Late-Onset Alzheimer's Disease from Mainland China PloS one 2015 10 e0144898 26680604 PMC4683047
  16. [18]Nacmias B Tedde A Bagnoli S Cellini E Guarnieri BM Piacentini S Sorbi S Implication of GAB2 gene polymorphism in Italian patients with Alzheimer's disease J Alzheimers Dis 2009 16 513 515 19276544
  17. [19]Lehmann DJ Wiebusch H Marshall SE Johnston C Warden DR Morgan K Schappert K Poirier J Xuereb J Kalsheker N Welsh KI Smith AD HLA class I, II & III genes in confirmed late-onset Alzheimer's disease Neurobiol Aging 2001 22 71 77 11164278
  18. [20]Shadfar S Hwang CJ Lim MS Choi DY Hong JT Involvement of inflammation in Alzheimer's disease pathogenesis and therapeutic potential of anti-inflammatory agents Arch Pharm Res 2015 38 2106 19 26289122
  19. [21]Serpente M Bonsi R Scarpini E Galimberti D Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment Neuroimmunomodulat 2014 21 79 87 24557039
  20. [22]International Parkinson Disease Genomics Consortium Nalls MA Plagnol V Hernandez DG Sharma M Sheerin UM Saad M Simon-Sanchez J Schulte C Lesage S Sveinbjornsdottir S Stefansson K Martinez M Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies Lancet 2011 377 641 649 21292315 PMC3696507
  21. [24]Yu L Chibnik LB Srivastava GP Pochet N Yang J Xu J Kozubek J Obholzer N Leurgans SE Schneider JA Meissner A De Jager PL Bennett DA Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease JAMA Neurol 2015 72 15 24 25365775 PMC4344367
  22. [25]McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease Neurology 1984 34 939 944 6610841

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Authors
Lu, R.-C., Yang, W., Tan, L., Sun, F.-R., Tan, M.-S., Zhang, W., Wang, H.-F., & Tan, L.
Affiliations
  • Qingdao University (CN)
  • Affiliated Hospital of Qingdao University (CN)
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-10-04
Volume
8
Issue
54
Pages
93219-93226
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.21479
PMC
PMC5696257
OpenAlex
W2764220275
Cited by
43
References
3
Citations by year
2026: 2 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 1 · 2018: 2
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Qingdao Key Health Discipline Development Fund
  • National Natural Science Foundation of China (81371406, 81501103, 81371406, 81571245, 81471309, 81371406, 81571245, and 81501103, 81471309, 81571245)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
HLA-DRB1, HLA-DRB1 polymorphism, late-onset Alzheimer's disease, genetic susceptibility, Han Chinese, APOE ε4, genetic association, replication study, meta-analysis, MHC class II, ethnic differences in genetic risk

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