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Single Nucleotide Polymorphism rs11136000 of CLU Gene (Clusterin, ApoJ) and the Risk of Late-Onset Alzheimer’s Disease in a Central European Population

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Abstract

Clusterin (CLU; also known as apolipoprotein J, ApoJ) is a protein of inconstant structure known to be involved in diverse processes inside and outside of brain cells. CLU can act as a protein chaperon or protein solubilizer, lipid transporter as well as redox sensor and be anti- or proapoptotic, depending on context. Primary structure of CLU is encoded by CLU gene which contains single nucleotide polymorphisms (SNP’s) associated with the risk of late-onset Alzheimer’s disease (LOAD). Studying a sample of Czech population and using the case-control association approach we identified C allele of the SNP rs11136000 as conferring a reduced risk of LOAD, more so in females than in males. Additionally, data from two smaller subsets of the population sample suggested a possible association of rs11136000 with diabetes mellitus. In a parallel study, we found no association between rs11136000 and mild cognitive impairment (MCI). Our findings on rs11136000 and LOAD contradict those of some previous studies done elsewhere. We discuss the multiple roles of CLU in a broad range of molecular mechanisms that may contribute to the variability of genetic studies of CLU in various ethnic groups. The above discordance notwithstanding, our conclusions support the association of rs1113600 with the risk of LOAD.

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Abbreviations

AD:

Alzheimer’s disease

ALOX5AP:

Arachidonate 5-lipoxygenase-activating protein

ApoE4:

Apolipoprotein E4

ApoJ:

Apolipoprotein J (a.k.a. clusterin)

BMI:

Body mass index

cCLU:

Cytoplasmic form of clusterin

CI:

Confidence interval

CLU:

Clusterin

CLU :

Gene encoding clusterin

CT:

Computed tomography

CVA:

Cerebrovascular accident

DM:

Diabetes mellitus

GWAS:

Genome-wide association study

LOAD:

Late-onset Alzheimer’s disease

MCI:

Mild cognitive impairment

MMSE:

Mini-mental state examination test

MoCA:

Montreal cognitive assessment

MS:

Manuscript

nCLU:

Nuclear form of clusterin

OR:

Odds ratio

PCR:

Polymerase chain reaction

RR:

Risk ratio

SBE:

Single base extension (reaction)

sCLU:

Secretory form of clusterin

SNP:

Single nucleotide polymorphisms

TNK1:

Tyrosine kinase non-receptor 1

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Acknowledgements

We would like to thank to Petr Ambroz and Ondřej Machaczka for organizing the collection of samples.

Funding

This work has been supported by Czech Health Research Council, Czech Republic (AZV CR)—grant projects No. NV18-04-00455 and 16-29900A.

Author information

Authors and Affiliations

  1. Bosch Institute and Discipline of Anatomy and Histology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia

    Vladimir J. Balcar

  2. Laboratory of Neurobiology and Pathological Physiology, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Veveří 97, 602 00, Brno, Czech Republic

    Vladimir J. Balcar, Tomáš Zeman, Jan Lochman & Omar Šerý

  3. Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

    Tomáš Zeman, Jan Lochman & Omar Šerý

  4. Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic

    Vladimír Janout & Jana Janoutová

  5. Present address: Faculty of Health Sciences, Palacký University Olomouc, Olomouc, Czech Republic

    Vladimír Janout & Jana Janoutová

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Contributions

VJB—writing, interpretation of results, final MS preparation; TZ—statistical analyses of data and interpretation, writing; JL—selection and design of laboratory methods, genetic analysis; VJ—conceptualisation, funding, patient enrolment; JJ—collection and curation of data; OS—conceptualisation, funding, laboratory analysis.

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Correspondence to Vladimir J. Balcar.

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Authors declare no conflicts of interest.

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All authors have read and approved the final version of the manuscript.

Ethical Approval

Informed consent was obtained from all participants or their legal representatives and formal approval for the study was granted by the Ethics Committee of the Faculty of Medicine, University of Ostrava, Czech Republic and by the Ethics Committee of St. Anne’s University Hospital, Brno, Czech Republic. The projects “Genetics and Epidemiology of Alzheimer’s Disease” (EK no. 11/2015), “Genetics and Epidemiology of Mild Cognitive Disorder” (EK no. 12/2015) were approved by the Committee on 16th June 2015 and project “The role of CD36 gene in pathogenesis of Alzheimer’s disease “was approved by the Ethics Committee of St. Anne’s University Hospital on 29th June 2017.

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Balcar, V.J., Zeman, T., Janout, V. et al. Single Nucleotide Polymorphism rs11136000 of CLU Gene (Clusterin, ApoJ) and the Risk of Late-Onset Alzheimer’s Disease in a Central European Population. Neurochem Res 46, 411–422 (2021). https://doi.org/10.1007/s11064-020-03176-y

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