Common genetic variations of deiodinase genes and prognosis of brain tumor patients
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ORIGINAL ARTICLE
Common genetic variations of deiodinase genes and prognosis of brain tumor patients Adomas Bunevicius 1,2,3 Edward R. Laws2,3 Ausra Saudargiene1 Arimantas Tamasauskas1 Giorgio Iervasi4 Vytenis Deltuva1 Timothy R. Smith2,3 Robertas Bunevicius5 ●
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Received: 19 April 2019 / Accepted: 11 July 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
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 thyroidstimulating 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. Keywords Glioma Deiodinase Glioblastoma Survival ●
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Introduction Thyroid hormones (THs) are important for normal brain development and tissue metabolism in healthy individuals and in severely ill patients. Activity of the Hypothalamicpituitary-thyroid (HPT) axis is closely controlled by the
* Adomas Bunevicius [email protected] 1
Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania
2
Brigham and Women’s Hospital, Boston, MA, USA
3
Harvard University, Boston, MA, USA
4
CNR - Institute of Clinical Physiology, Pisa, Italy
5
Lithuanian University of Health Sciences, Kaunas, Lithuania
hypothalamic thyrotropin-releasing hormone (TRH) and via negative feedback of circulating THs on the hypothalamus and pituitary gland. TRH stimulates the anterior pituitary gland to synthetize and release thyroid-stimulating hormone (TSH) that in turn activates the thyroid gland
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