The -258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH

作者：Maya Y Peltsverger, Peter W Butler, Anna Teresa Alberobello, Susan M. Smith, Yanina Guevara, Ornella M. Dubaz, Javier Armando Luzon, Joyce D. Linderman, Francesco Saverio Celi · 发表于：European Journal of Endocrinology · 年份：2012 · DOI：10.1530/eje-11-1073 · 被引用次数：29 · 研究领域：Thyroid Disorders and Treatments、Thyroid Cancer Diagnosis and Treatment、Growth Hormone and Insulin-like Growth Factors

OBJECTIVE: 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. DESIGN: Retrospective analysis. METHODS: The TH secretion in response to 500 μg i.v. TRH injection was studied in 45 healthy volunteers. RESULTS: 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. CONCLUSIONS: 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 ch...