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 …
MY Peltsverger, PW Butler… - European journal of …, 2012 - academic.oup.com
MY Peltsverger, PW Butler, AT Alberobello, S Smith, Y Guevara, OM Dubaz, JA Luzon…
European journal of endocrinology, 2012•academic.oup.comObjective 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
(T4) to triiodothyronine (T3) conversion and thyroid hormone (TH) secretion pattern, we
studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland. Design …
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
(T4) to triiodothyronine (T3) conversion and thyroid hormone (TH) secretion pattern, we
studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland. Design …
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 (T4) to triiodothyronine (T3) 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 T3 levels were observed, carriers of the −258G/x allele showed a blunted rise in free T4 (FT4; P<0.01). The −258G/x 92Thr/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 FT4 secretion with a normal T3 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.
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