Skip to main content
SpringerLink
Log in

Association of Single Nucleotide Polymorphism at rs2275294 in the ZNF512B Gene with Prognosis in Amyotrophic Lateral Sclerosis

  • Rapid Communications
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

The aim of this study is to explore whether the single nucleotide polymorphism rs2275294 in the ZNF512B gene is related to the length of survival of patients with amyotrophic lateral sclerosis (ALS). This prospective study examined 212 patients with ALS, who were genotyped at the rs2275294 locus in ZNF512B using the ligase method. Genotype was compared with clinical data and survival. Kaplan–Meier survival analysis and Cox hazard regression were used to identify risk factors of shorter survival. Our results were meta-analyzed together with previous work in order to examine the potential association between the rs2275294-C allele and survival. Of the 212 patients, 166 carried the CC + CT genotype at the rs2275294 locus, while 46 carried the TT genotype. Patients with the C allele showed significantly shorter survival than those without it (34.13 ± 1.9 vs. 45.32 ± 5.7 months, p = 0.036). Cox analysis identified the C allele and time from symptom onset to diagnosis as risk factors for shorter survival. Meta-analysis of 447 patients in China and Japan confirmed the rs2275294-C allele to be an independent risk factor of shorter survival in ALS patients. The C allele at the rs2275294 locus in ZNF512B is a risk factor for shorter survival in patients with ALS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  • Brooks, B. R., Miller, R. G., Swash, M., & Munsat, T. L. (2000). World Federation of Neurology Research Group on Motor Neuron D. El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 1(5), 293–299.

    Article  CAS  Google Scholar 

  • Chia, R., Chio, A., & Traynor, B. J. (2018). Novel genes associated with amyotrophic lateral sclerosis: Diagnostic and clinical implications. The Lancet Neurology, 17(1), 94–102.

    Article  CAS  Google Scholar 

  • Day, W. A., Koishi, K., Nukuda, H., & McLennan, I. S. (2005). Transforming growth factor-beta 2 causes an acute improvement in the motor performance of transgenic ALS mice. Neurobiology of Disease, 19(1–2), 323–330.

    Article  CAS  Google Scholar 

  • Duque, T., Gromicho, M., Pronto-Laborinho, A. C., & de Carvalho, M. (2020). Transforming growth factor-beta plasma levels and its role in amyotrophic lateral sclerosis. Medical Hypotheses, 139, 109632.

    Article  CAS  Google Scholar 

  • Higgins, J. P., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414), 557–560.

    Article  Google Scholar 

  • Houi, K., Kobayashi, T., Kato, S., Mochio, S., & Inoue, K. (2002). Increased plasma TGF-beta1 in patients with amyotrophic lateral sclerosis. Acta Neurologica Scandinavica, 106(5), 299–301.

    Article  CAS  Google Scholar 

  • Iida, A., Takahashi, A., Kubo, M., Saito, S., Hosono, N., Ohnishi, Y., et al. (2011). A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese. Human Molecular Genetics, 20(18), 3684–3692.

    Article  CAS  Google Scholar 

  • Masrori, P., & Van Damme, P. (2020). Amyotrophic lateral sclerosis: A clinical review. European Journal of Neurology. https://doi.org/10.1111/ene.14393.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mejzini, R., Flynn, L. L., Pitout, I. L., Fletcher, S., Wilton, S. D., & Akkari, P. A. (2019). ALS genetics, mechanisms, and therapeutics: Where are we now? Frontiers in Neuroscience, 13, 1310.

    Article  Google Scholar 

  • Ning, P., Yang, X., Yang, B., Zhao, Q., Huang, H., An, R., et al. (2018). Meta-analysis of the association between ZNF512B polymorphism rs2275294 and risk of amyotrophic lateral sclerosis. Neurological Sciences, 39(7), 1261–1266.

    Article  Google Scholar 

  • Nowicka, N., Juranek, J., Juranek, J. K., & Wojtkiewicz, J. (2019). Risk factors and emerging therapies in amyotrophic lateral sclerosis. International Journal of Molecular Sciences, 20(11), 2616.

    Article  CAS  Google Scholar 

  • Schober, A., Peterziel, H., von Bartheld, C. S., Simon, H., Krieglstein, K., & Unsicker, K. (2007). GDNF applied to the MPTP-lesioned nigrostriatal system requires TGF-beta for its neuroprotective action. Neurobiology of Disease, 25(2), 378–391.

    Article  CAS  Google Scholar 

  • Tetsuka, S., Morita, M., Iida, A., Uehara, R., Ikegawa, S., & Nakano, I. (2013). ZNF512B gene is a prognostic factor in patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences, 324(1–2), 163–166.

    Article  CAS  Google Scholar 

  • Thomas, G., Sinville, R., Sutton, S., Farquar, H., Hammer, R. P., Soper, S. A., et al. (2004). Capillary and microelectrophoretic separations of ligase detection reaction products produced from low-abundant point mutations in genomic DNA. Electrophoresis, 25(10–11), 1668–1677.

    Article  CAS  Google Scholar 

  • van Es, M. A., Van Vught, P. W., Blauw, H. M., Franke, L., Saris, C. G., Andersen, P. M., et al. (2007). ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: A genome-wide association study. The Lancet Neurology., 6(10), 869–877.

    Article  Google Scholar 

  • van Es, M. A., Veldink, J. H., Saris, C. G., Blauw, H. M., van Vught, P. W., Birve, A., et al. (2009). Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nature Genetics, 41(10), 1083–1087.

    Article  Google Scholar 

  • Westeneng, H. J., Debray, T. P. A., Visser, A. E., van Eijk, R. P. A., Rooney, J. P. K., Calvo, A., et al. (2018). Prognosis for patients with amyotrophic lateral sclerosis: Development and validation of a personalised prediction model. The Lancet Neurology, 17(5), 423–433.

    Article  Google Scholar 

  • Yang, B., Jiang, H., Wang, F., Li, S., Wu, C., Bao, J., et al. (2019). UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: A meta-analysis. Neurological Sciences, 40(11), 2293–2302.

    Article  Google Scholar 

  • Yang, X., Zhao, Q., An, R., Zheng, J., Tian, S., & Xu, Y. (2015). Association of the functional SNP rs2275294 in ZNF512B with risk of amyotrophic lateral sclerosis and Parkinson’s disease in Han Chinese. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration, 17(1–2), 142–147.

    Google Scholar 

  • Yang, X., Zheng, J., Tian, S., Chen, Y., An, R., Zhao, Q., et al. (2017). HLA-DRA/HLA-DRB5 polymorphism affects risk of sporadic ALS and survival in a southwest Chinese cohort. Journal of the Neurological Sciences, 373, 124–128.

    Article  CAS  Google Scholar 

  • Yu, C. J., Wang, L., Mao, S. L., Zhang, Y., Song, L. L., Cai, L. Y., et al. (2018). The clinical assessment of amyotrophic lateral sclerosis patients’ prognosis by ZNF512B gene, neck flexor muscle power score and body mass index (BMI). BMC Neurology, 18(1), 211.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by the National Natural Science Foundation of China (81960242), Yunnan Applied Basic Research Project (2019FE001-048,202001AT070001), Yunnan Provincial Health Science and Technology Project (2018NS0102), The Applied basic Research of The Diagnosis and Treatment Center of Neurological Diseases in Yunnan Province (ZX2019-03-05), and 100 Young and Middle-aged Academic and Technical Scholars at Kunming Medical University (60118260105).

Author information

Author notes

  1. Haixia Jiang, Baiyuan Yang and Fang Wang contribute equally.

Authors and Affiliations

  1. Department of Anesthesia, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, People’s Republic of China

    Haixia Jiang

  2. Department of Neurology, Seventh People’s Hospital of Chengdu, Chengdu, 690041, Sichuan, People’s Republic of China

    Baiyuan Yang

  3. Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, People’s Republic of China

    Fang Wang, Kelu Li, Yongyun Zhu, Bin Liu, Hui Ren & Xinglong Yang

  4. Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Sijia Tian & Yanming Xu

  5. Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, People’s Republic of China

    Ailan Pang

Authors
  1. Haixia Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baiyuan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kelu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongyun Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hui Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sijia Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yanming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ailan Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xinglong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ailan Pang or Xinglong Yang.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, H., Yang, B., Wang, F. et al. Association of Single Nucleotide Polymorphism at rs2275294 in the ZNF512B Gene with Prognosis in Amyotrophic Lateral Sclerosis. Neuromol Med 23, 242–246 (2021). https://doi.org/10.1007/s12017-020-08634-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-020-08634-y

Keywords

Search

Navigation