Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Eur J Endocrinol. 2012 May;166(5):839-45. doi: 10.1530/EJE-11-1073. Epub 2012 Feb 3.
Type 2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The -258A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of -258A/G polymorphism on intrathyroidal thyroxine (T(4)) to triiodothyronine (T(3)) conversion and thyroid hormone (TH) secretion pattern, we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland.
Retrospective analysis.
The TH secretion in response to 500 μg i.v. TRH injection was studied in 45 healthy volunteers.
Twenty-six subjects (16 females and ten males, 32.8 ± 10.4 years) were homozygous for the ancestral (-258A/A) allele and 19 (11 females and eight males, 31.1 ± 10.9 years) were carriers of the (-258G/x) variant. While no differences in the peak TSH and T(3) levels were observed, carriers of the -258G/x allele showed a blunted rise in free T(4) (FT(4); P<0.01). The -258G/x92Thr/Thr haplotype, compared with the other groups, had lower TSH values at 60 min (P<0.03). No differences were observed between genotypes in baseline TH levels.
The -258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated FT(4) secretion with a normal T(3) release from the thyroid gland consistent with a shift in the reaction equilibrium toward the product. These data indicate that the -258G DIO2 polymorphism causes changes in the pattern of hormone secretion. These findings are a proof of concept that common polymorphisms in DIO2 can subtly affect the circulating levels of TH and might modulate the TH homeostasis.
2 型脱碘酶基因（DIO2）多态性与垂体-甲状腺轴稳态的变化有关。-258A/G（SNP rs12885300）多态性与酶活性增加有关，但数据存在矛盾。为了描述-258A/G 多态性对甲状腺内甲状腺素（T4）向三碘甲状腺原氨酸（T3）转化和甲状腺激素（TH）分泌模式的影响，我们研究了急性、TRH 介导、TSH 刺激甲状腺的作用。
回顾性分析。
研究了 45 名健康志愿者对 500μg 静脉注射 TRH 反应的 TH 分泌情况。
26 名受试者（16 名女性和 10 名男性，32.8±10.4 岁）为原始（-258A/A）等位基因纯合子，19 名（11 名女性和 8 名男性，31.1±10.9 岁）为（-258G/x）变体携带者。虽然 TSH 和 T3 水平的峰值无差异，但携带-258G/x 等位基因的个体显示游离 T4（FT4）的上升幅度较低（P<0.01）。与其他组相比，-258G/x92Thr/Thr 单倍型在 60 分钟时 TSH 值较低（P<0.03）。基因型之间的基础 TH 水平无差异。
-258G/x DIO2 多态性变异与急性 TSH 刺激 FT4 分泌率降低有关，甲状腺中 T3 释放正常，表明反应平衡向产物方向移动。这些数据表明，-258G DIO2 多态性导致激素分泌模式的变化。这些发现证明了 DIO2 中的常见多态性可以微妙地影响 TH 的循环水平，并可能调节 TH 的稳态。
