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

Autor: Bunevicius A; Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania. a.bunevicius@yahoo.com.; Brigham and Women's Hospital, Boston, MA, USA. a.bunevicius@yahoo.com.; Harvard University, Boston, MA, USA. a.bunevicius@yahoo.com., Laws ER; Brigham and Women's Hospital, Boston, MA, USA.; Harvard University, Boston, MA, USA., Saudargiene A; Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania., Tamasauskas A; Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania., Iervasi G; CNR - Institute of Clinical Physiology, Pisa, Italy., Deltuva V; Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania., Smith TR; Brigham and Women's Hospital, Boston, MA, USA.; Harvard University, Boston, MA, USA., Bunevicius R; Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jazyk: angličtina
Zdroj: Endocrine [Endocrine] 2019 Dec; Vol. 66 (3), pp. 563-572. Date of Electronic Publication: 2019 Aug 26.
DOI: 10.1007/s12020-019-02016-6
Abstrakt: 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.
Databáze: MEDLINE
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