Skip to main content
SpringerLink
Log in

Common genetic variations of deiodinase genes and prognosis of brain tumor patients

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Background

Thyroid hormone (TH) metabolism can have prognostic significance in brain tumors. We studied the association of common variations in three deiodinase gene single-nucleotide polymorphisms (SNPs) with circulating TH concentrations and prognosis of brain tumor patients.

Methods

Patients admitted for glioma and meningioma surgery between January, 2010 and September, 2011 were evaluated for functional status (Barthel Index or BI) and circulating free tri-iodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) concentrations. Ten common SNPs in the DIO1 gene; five SNPs in the DIO2 gene; and one SNP in the DIO3 gene were genotyped. Follow-up continued until November, 2017.

Results

In glioblastoma patients, the DIO1 SNP rs2235544 CC genotype was associated with significantly lower risk of death at 2 years when compared to AA + CA genotypes after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, and extent of resection (HR = 0.34, 95% CI: 0.13–0.84, p = 0.019). The TT genotype vs. CC + TC genotypes of the DI02 SNP rs12885300 was associated with increased mortality risk after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, extent of resection, and FT3/FT4 (HR = 3.13, 95% CI: 1.20–8.16, p < 0.019). The C-allele of the DI01 SNP rs2235544 was related to increased circulating free T3/ free T4 ratio in glioma and meningioma patients, indicating greater T4 to T3 conversion.

Conclusions

SNPs of DIO1 gene (rs2235544) and DIO2 gene (rs12885300) have independent prognostic significance in glioblastoma patients. The C-allele of the DIO1 (rs2235544) is associated with greater T4 to T3 conversion.

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

Similar content being viewed by others

References

  1. A.C. Bianco, D. Salvatore, B. Gereben, M.J. Berry, P.R. Larsen, Endocr. Rev. 23, 38 (2002)

    Article  CAS  Google Scholar 

  2. M.H. Warner, G.J. Beckett, J. Endocrinol. 205, 1 (2010)

    Article  CAS  Google Scholar 

  3. J.E. Silva, P.R. Larsen, J. Clin. Invest. 70, 1110 (1982)

    Article  CAS  Google Scholar 

  4. W.E. Visser, E.C.H. Friesema, J. Jansen, T.J. Visser, Trends Endocrinol. Metab. 19, 50 (2008)

    Article  CAS  Google Scholar 

  5. C.M. Dayan, V. Panicker, Nat. Rev. Endocrinol. 5, 211 (2009)

    Article  CAS  Google Scholar 

  6. H. Verloop, O.M. Dekkers, R.P. Peeters, J.W. Schoones, J.W.A. Smit, Eur. J. Endocrinol. 171, R123 (2014)

    Article  CAS  Google Scholar 

  7. G. Van den Berghe, Thyroid 24, 1456 (2014)

    Article  Google Scholar 

  8. X. Jiang, H. Xing, J. Wu, R. Du, H. Liu, J. Chen, J. Wang, C. Wang, Y. Wu, Sci. Rep. 7, 16256 (2017)

    Article  Google Scholar 

  9. R. Gao, J.-H. Liang, L. Wang, H.-Y. Zhu, W. Wu, J.-Z. Wu, Y. Xia, L. Cao, L. Fan, T. Yang, J.-Y. Li, W. Xu, Br. J. Haematol. 177, 95 (2017)

    Article  CAS  Google Scholar 

  10. L.J. DeGroot, The Non-Thyroidal Illness Syndrome. In: Feingold, K.R. Anawalt, B. Boyce, A. Chrousos, G. Dungan, K. Grossman, A. Hershman, J.M. Kaltsas, G. Koch, C. Kopp, P. Korbonits, M. McLachlan, R. Morley, J.E. New, M. Perreault, L. Purnell, J. Rebar, R. Singer, F. Trence, D.L. Vinik, A. Wilson, D.P. (Eds), Endotext. MDText.com, Inc., South Dartmouth, MA (2000).

  11. A.L. Maia, I.M. Goemann, E.L.S. Meyer, S.M. Wajner, J. Endocrinol. 209, 283 (2011)

    Article  CAS  Google Scholar 

  12. A. Bunevicius, E.R. Laws, V. Deltuva, A. Tamasauskas, J. Neurooncol. 131, 385 (2017)

    Article  CAS  Google Scholar 

  13. A. Bunevicius, V. Deltuva, S. Tamasauskas, A. Tamasauskas, E.R. Laws, R. Bunevicius, J. Neurosurg. 118, 1279 (2013)

    Article  CAS  Google Scholar 

  14. A. Bunevicius, V.P. Deltuva, S. Tamasauskas, T. Smith, E.R. Laws, R. Bunevicius, G. Iervasi, A. Tamasauskas, Oncotarget 8, 8648 (2017)

    PubMed  Google Scholar 

  15. C. Perrotta, C. De Palma, E. Clementi, D. Cervia, Front. Cell. Neurosci. 9, 236 (2015)

    Article  Google Scholar 

  16. A. Liappas, L. Alexandros, I. Mourouzis, M. Iordanis, A. Zisakis, Z. Athanasios, K. Economou, E. Konstantinos, R.-W. Lea, L. Robert-William, C. Pantos, P. Constantinos, J. Thyroid Res. 2011, 856050 (2011)

    PubMed  Google Scholar 

  17. F.I. Mahoney, D.W. Barthel, Md State Med. J. 14, 61 (1965)

    CAS  PubMed  Google Scholar 

  18. S. Rodriguez, T.R. Gaunt, I.N.M. Day, Am. J. Epidemiol. 169, 505 (2009)

    Article  Google Scholar 

  19. T.R. Gaunt, S. Rodríguez, I.N. Day, BMC Bioinform. 8, 428 (2007)

    Article  Google Scholar 

  20. V. Panicker, C. Cluett, B. Shields, A. Murray, K.S. Parnell, J.R.B. Perry, M.N. Weedon, A. Singleton, D. Hernandez, J. Evans, C. Durant, L. Ferrucci, D. Melzer, P. Saravanan, T.J. Visser, G. Ceresini, A.T. Hattersley, B. Vaidya, C.M. Dayan, T.M. Frayling, J. Clin. Endocrinol. Metab. 93, 3075 (2008)

    Article  CAS  Google Scholar 

  21. E. Porcu, M. Medici, G. Pistis, C.B. Volpato, S.G. Wilson, A.R. Cappola, S.D. Bos, J. Deelen, M. den Heijer, R.M. Freathy, J. Lahti, C. Liu, L.M. Lopez, I.M. Nolte, J.R. O’Connell, T. Tanaka, S. Trompet, A. Arnold, S. Bandinelli, M. Beekman, S. Böhringer, S.J. Brown, B.M. Buckley, C. Camaschella, A.J.M. de Craen, G. Davies, M.C.H. de Visser, I. Ford, T. Forsen, T.M. Frayling, L. Fugazzola, M. Gögele, A.T. Hattersley, A.R. Hermus, A. Hofman, J.J. Houwing-Duistermaat, R.A. Jensen, E. Kajantie, M. Kloppenburg, E.M. Lim, C. Masciullo, S. Mariotti, C. Minelli, B.D. Mitchell, R. Nagaraja, R.T. Netea-Maier, A. Palotie, L. Persani, M.G. Piras, B.M. Psaty, K. Räikkönen, J.B. Richards, F. Rivadeneira, C. Sala, M.M. Sabra, N. Sattar, B.M. Shields, N. Soranzo, J.M. Starr, D.J. Stott, F.C.G.J. Sweep, G. Usala, M.M. van der Klauw, D. van Heemst, A. van Mullem, S.H. Vermeulen, W.E. Visser, J.P. Walsh, R.G.J. Westendorp, E. Widen, G. Zhai, F. Cucca, I.J. Deary, J.G. Eriksson, L. Ferrucci, C.S. Fox, J.W. Jukema, L.A. Kiemeney, P.P. Pramstaller, D. Schlessinger, A.R. Shuldiner, E.P. Slagboom, A.G. Uitterlinden, B. Vaidya, T.J. Visser, B.H.R. Wolffenbuttel, I. Meulenbelt, J.I. Rotter, T.D. Spector, A.A. Hicks, D. Toniolo, S. Sanna, R.P. Peeters, S. Naitza. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS Genet 9, e1003266 (2013)

  22. H.F. Escobar-Morreale, M.J. Obregón, F. Escobar del Rey, G. Morreale de Escobar, J. Clin. Invest. 96, 2828 (1995)

    Article  CAS  Google Scholar 

  23. H.C. Hoftijzer, K.A. Heemstra, T.J. Visser, S. le Cessie, R.P. Peeters, E.P.M. Corssmit, J.W.A. Smit, J. Clin. Endocrinol. Metab. 96, E1527 (2011)

    Article  CAS  Google Scholar 

  24. M.Y. Peltsverger, P.W. Butler, A.T. Alberobello, S. Smith, Y. Guevara, O.M. Dubaz, J.A. Luzon, J. Linderman, F.S. Celi, Eur. J. Endocrinol. 166, 839 (2012)

    Article  CAS  Google Scholar 

  25. S.-F. Ma, L. Xie, M. Pino-Yanes, S. Sammani, M.S. Wade, E. Letsiou, J. Siegler, T. Wang, G. Infusino, R.A. Kittles, C. Flores, T. Zhou, B.S. Prabhakar, L. Moreno-Vinasco, J. Villar, J.R. Jacobson, S.M. Dudek, J.G.N. Garcia, Am. J. Respir. Cell Mol. Biol. 45, 1203 (2011)

    Article  CAS  Google Scholar 

  26. R.P. Peeters, H. van Toor, W. Klootwijk, Y.B. de Rijke, G.G.J.M. Kuiper, A.G. Uitterlinden, T.J. Visser, J. Clin. Endocrinol. Metab. 88, 2880 (2003)

    Article  CAS  Google Scholar 

  27. R.P. Peeters, A.W. van den Beld, H. Attalki, H. van Toor, Y.B. de Rijke, G.G.J.M. Kuiper, S.W.J. Lamberts, J.A.M.J.L. Janssen, A.G. Uitterlinden, T.J. Visser, Am. J. Physiol. Endocrinol. Metab. 289, E75 (2005)

    Article  CAS  Google Scholar 

Download references

Funding

The study was supported by the Research Council of Lithuania (grant number: MIP-044/2015).

Author contributions

RB and AB designed the study; AB, AT and VD acquired the data; AB, AS, ERL, GI, TRS analyzed the data; AB and AS wrote the manuscript; All authors critically reviewed the manuscript.

Author information

Authors and Affiliations

  1. Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania

    Adomas Bunevicius, Ausra Saudargiene, Arimantas Tamasauskas & Vytenis Deltuva

  2. Brigham and Women’s Hospital, Boston, MA, USA

    Adomas Bunevicius, Edward R. Laws & Timothy R. Smith

  3. Harvard University, Boston, MA, USA

    Adomas Bunevicius, Edward R. Laws & Timothy R. Smith

  4. CNR - Institute of Clinical Physiology, Pisa, Italy

    Giorgio Iervasi

  5. Lithuanian University of Health Sciences, Kaunas, Lithuania

    Robertas Bunevicius

Authors
  1. Adomas Bunevicius
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edward R. Laws
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ausra Saudargiene
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arimantas Tamasauskas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giorgio Iervasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vytenis Deltuva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Timothy R. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robertas Bunevicius
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adomas Bunevicius.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict 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

Bunevicius, A., Laws, E.R., Saudargiene, A. et al. Common genetic variations of deiodinase genes and prognosis of brain tumor patients. Endocrine 66, 563–572 (2019). https://doi.org/10.1007/s12020-019-02016-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-019-02016-6

Keywords

Search

Navigation