Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Brigham and Women's Hospital, Boston, MA, USA.
Endocrine. 2019 Dec;66(3):563-572. doi: 10.1007/s12020-019-02016-6. Epub 2019 Aug 26.
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.
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.
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.
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.
甲状腺激素（TH）代谢在脑肿瘤中具有预后意义。我们研究了三个脱碘酶基因单核苷酸多态性（SNP）的常见变异与脑肿瘤患者循环 TH 浓度和预后的关系。
2010 年 1 月至 2011 年 9 月期间，评估接受神经胶质瘤和脑膜瘤手术的患者的功能状态（巴氏指数或 BI）和循环游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）和促甲状腺激素（TSH）浓度。在 DIO1 基因中检测了 10 个常见 SNP；DIO2 基因中的 5 个 SNP；以及 DIO3 基因中的 1 个 SNP。随访持续到 2017 年 11 月。
在胶质母细胞瘤患者中，与 AA+CA 基因型相比，DIO1 基因 rs2235544CC 基因型患者在调整患者性别、年龄、术前功能状态、辅助治疗和切除范围后，2 年死亡风险显著降低（HR=0.34，95%CI：0.13-0.84，p=0.019）。调整患者性别、年龄、术前功能状态、辅助治疗、切除范围和 FT3/FT4 后，DIO2 基因 rs12885300 的 TT 基因型与 CC+TC 基因型相比，死亡风险增加（HR=3.13，95%CI：1.20-8.16，p<0.019）。DIO1 基因 rs2235544 的 C 等位基因与胶质母细胞瘤和脑膜瘤患者循环游离 T3/游离 T4 比值增加有关，表明 T4 向 T3 的转化率增加。
DIO1 基因（rs2235544）和 DIO2 基因（rs12885300）的 SNP 在胶质母细胞瘤患者中有独立的预后意义。DIO1（rs2235544）的 C 等位基因与更大的 T4 向 T3 转化率有关。
