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Study of Deiodinase Type 2 Polymorphisms in Graves' Disease and Ophthalmopathy in a Swedish Population

Shahida, Bushra LU ; Planck, Tereza LU ; Åsman, Peter LU and Lantz, Mikael LU (2018) In European Thyroid Journal 7(6). p.289-293
Abstract

Background: 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. Objectives: The aim of the study was to examine whether SNPs in DIO2 are associated with GD or Graves' ophthalmopathy (GO). Methods: 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... (More)

Background: 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. Objectives: The aim of the study was to examine whether SNPs in DIO2 are associated with GD or Graves' ophthalmopathy (GO). Methods: 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 (n = 311) or without (n = 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). Results: Rs225011 was nominally associated with GD (OR 1.18, CI 1.01-1.37, p = 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. Conclusions: 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.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Deiodinase type 2, Free T3, Graves' disease, Graves' ophthalmopathy, rs12885300, rs225011, rs225014, Single nucleotide polymorphism, Thr92Ala, Thyroid-stimulating hormone receptor antibodies
in
European Thyroid Journal
volume
7
issue
6
pages
5 pages
publisher
Karger
external identifiers
  • pmid:30574458
  • scopus:85057317886
ISSN
2235-0640
DOI
10.1159/000490892
language
English
LU publication?
yes
id
f3701e72-412a-492c-b52c-ddd795ca7fca
date added to LUP
2018-12-05 13:36:17
date last changed
2024-01-30 04:29:10
@article{f3701e72-412a-492c-b52c-ddd795ca7fca,
  abstract     = {{<p>Background: 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. Objectives: The aim of the study was to examine whether SNPs in DIO2 are associated with GD or Graves' ophthalmopathy (GO). Methods: 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 (n = 311) or without (n = 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). Results: Rs225011 was nominally associated with GD (OR 1.18, CI 1.01-1.37, p = 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. Conclusions: 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.</p>}},
  author       = {{Shahida, Bushra and Planck, Tereza and Åsman, Peter and Lantz, Mikael}},
  issn         = {{2235-0640}},
  keywords     = {{Deiodinase type 2; Free T3; Graves' disease; Graves' ophthalmopathy; rs12885300; rs225011; rs225014; Single nucleotide polymorphism; Thr92Ala; Thyroid-stimulating hormone receptor antibodies}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{289--293}},
  publisher    = {{Karger}},
  series       = {{European Thyroid Journal}},
  title        = {{Study of Deiodinase Type 2 Polymorphisms in Graves' Disease and Ophthalmopathy in a Swedish Population}},
  url          = {{http://dx.doi.org/10.1159/000490892}},
  doi          = {{10.1159/000490892}},
  volume       = {{7}},
  year         = {{2018}},
}