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Polymorphism rs11867353 of Tyrosine Kinase Non-Receptor 1 (TNK1) Gene Is a Novel Genetic Marker for Alzheimer’s Disease

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Abstract

Several single-nucleotide polymorphisms (SNPs) and rare variants of non-receptor tyrosine kinase 1 gene (TNK1) have been associated with Alzheimer’s disease (AD). To date, none of the associations have proven to be of practical importance in predicting the risk of AD either because the evidence is not conclusive, or the risk alleles occur at very low frequency. In the present study, we are evaluating the associations between rs11867353 polymorphism of TNK1 gene and both AD and mild cognitive impairment (MCI) in a group of 1656 persons. While the association with AD was found to be highly statistically significant (p < 0.0001 for the risk genotype CC), no statistically significant association with MCI could be established. Possible explanation of the apparent discrepancy could be rapid progression of MCI to AD in persons with the CC genotype. Additional findings of the study are statistically significant associations of rs11867353 polymorphism with body mass index, body weight, and body height. The patients with AD and CC genotype had significantly lower values of body mass index and body weight compared with patients with other genotypes. The main outcome of the study is the finding of a previously never described association between the rs11867353 polymorphism of the TNK1 gene and AD. The rs11867353 polymorphism has a potential to become a significant genetic marker when predicting the risk of AD.

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Acknowledgments

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

Funding

This work has been supported by the Agency for Healthcare Research, Czech Republic (AZV CR)—grant project No. 16-29900A.

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Authors and Affiliations

  1. 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

    Tomáš Zeman, Jan Lochman & Omar Šerý

  2. 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

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

    Kamila Cahová, Jan Lochman & Omar Šerý

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

    Jana Janoutová & Vladimír Janout

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  1. Tomáš Zeman
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  2. Vladimir J. Balcar
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  3. Kamila Cahová
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  4. Jana Janoutová
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  5. Vladimír Janout
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  6. Jan Lochman
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  7. Omar Šerý
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Contributions

Tomáš Zeman: writing—original draft preparation, software, formal analysis, visualization. Vladimir J. Balcar: writing—reviewing and editing, conceptualization. Kamila Cahová: investigation. Jana Janoutová: resources. Vladimír Janout: resources, funding acquisition. Jan Lochman: methodology. Omar Šerý: conceptualization, funding acquisition, resources, methodology, project administration, writing—reviewing and editing.

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Correspondence to Omar Šerý.

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Approval was obtained from the ethics committee of the Faculty of Medicine, University of Ostrava, Czech Republic. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Zeman, T., Balcar, V.J., Cahová, K. et al. Polymorphism rs11867353 of Tyrosine Kinase Non-Receptor 1 (TNK1) Gene Is a Novel Genetic Marker for Alzheimer’s Disease. Mol Neurobiol 58, 996–1005 (2021). https://doi.org/10.1007/s12035-020-02153-4

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