Shahida Bushra, Planck Tereza, Åsman Peter, Lantz Mikael
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malmö, Sweden.
Department of Diabetes and Endocrinology, Skåne University Hospital, Malmö, Sweden.
Eur Thyroid J. 2018 Nov;7(6):289-293. doi: 10.1159/000490892. Epub 2018 Jul 20.
Deiodinase type 2 (DIO2) is an enzyme that catalyzes the production of the active form of thyroid -hormone triiodothyronine (T3) from thyroxine (T4) and is important for maintaining intracellular T3 levels. Single nucleotide polymorphisms (SNPs) in DIO2 were associated with several diseases. The association of SNPs in DIO2 with Graves' disease (GD) was suggested in 2 Russian studies.
The aim of the study was to examine whether SNPs in DIO2 are associated with GD or Graves' ophthalmopathy (GO).
Seven SNPs in the DIO2 gene - rs225014 (Thr92Ala), rs12885300, rs2267872, rs225011, rs224995, rs225015, and rs2267873 - were studied to assess their association with GD and GO. In total, 712 patients with GD with ( = 311) or without ( = 399) ophthalmopathy and 1,183 sex-matched controls from Malmö, Sweden were analyzed. In GD patients with available data, the SNPs were examined for association with the levels of free T3, free T4, thyroid-stimulating hormone receptor antibodies (TRAb), and thyroid-peroxidase antibodies (TPOAb).
Rs225011 was nominally associated with GD (OR 1.18, CI 1.01-1.37, = 0.036). None of the SNPs were associated with GO. In GD patients, none of the SNPs were associated with the free-T4 (fT4), TRAb, or TPOAb levels. A weak, nonsignificant association was observed between free-T3 (fT3) levels and rs225014 and rs12885300, separately.
Rs225011 in DIO2 was weakly associated with GD. The mechanism behind this association requires further study. None of the investigated common SNPs in DIO2 was significantly associated with GO, fT3, fT4, TRAb, or TPOAb in GD patients.
2型脱碘酶（DIO2）是一种催化从甲状腺素（T4）生成甲状腺激素三碘甲状腺原氨酸（T3）活性形式的酶，对维持细胞内T3水平很重要。DIO2中的单核苷酸多态性（SNP）与多种疾病相关。两项俄罗斯研究提示DIO2中的SNP与格雷夫斯病（GD）有关。
本研究旨在探讨DIO2中的SNP是否与GD或格雷夫斯眼病（GO）相关。
研究了DIO2基因中的7个SNP——rs225014（Thr92Ala）、rs12885300、rs2267872、rs225011、rs224995、rs225015和rs2267873——以评估它们与GD和GO的相关性。总共分析了来自瑞典马尔默的712例患有（n = 311）或未患有（n = 399）眼病的GD患者以及1183名性别匹配的对照。在有可用数据的GD患者中，研究了这些SNP与游离T3、游离T4、促甲状腺激素受体抗体（TRAb）和甲状腺过氧化物酶抗体（TPOAb）水平的相关性。
Rs225011与GD存在名义上的相关性（OR 1.18，CI 1.01 - 1.37，P = 0.036）。没有一个SNP与GO相关。在GD患者中，没有一个SNP与游离T4（fT4）、TRAb或TPOAb水平相关。游离T3（fT3）水平与rs225014和rs12885300分别存在微弱的、无统计学意义的相关性。
DIO2中的Rs225011与GD存在弱相关性。这种关联背后的机制需要进一步研究。在GD患者中，所研究的DIO2常见SNP均与GO、fT3、fT4、TRAb或TPOAb无显著相关性。
