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- Title
Identification and Consequences of Polymorphisms in the Thyroid Hormone Receptor Alpha and Beta Genes.
- Authors
Helena Gásdal Sørensen; Wendy M. van der Deure; Pia Skov Hansen; Robin P. Peeters; Monique M.B. Breteler; Kirsten Ohm Kyvik; Thorkild I.A. Sørensen; Laszlo Hegedüs; Theo J. Visser
- Abstract
Objective:Genetic factors exert considerable influence on thyroid function variables. Single nucleotide polymorphisms (SNPs) in thyroid hormone pathway genes have been associated with serum thyroid parameters implying small alterations in the hypothalamusâpituitaryâthyroid axis. However, little is known about SNPs in the THRA(17q11.2) and THRB(3p24.2) genes. The aim of this study was to map THRAand THRBfor the occurrence and frequencies of SNPs and relate these to thyroid parameters.Design and Methods:SNPs were identified by sequencing all THRAand THRBexons and flanking regions in 52 randomly selected subjects. SNPs were genotyped in 1116 healthy Danish twins by TaqMan assays and related to thyroid parameters. One SNP in THRBwas additionally genotyped in the elderly population of the Rotterdam Scan Study (n 940).Main Outcome:15 SNPs (7 novel) in THRAand THRBwere identified. Two SNPs in the 3â² untranslated region of THRAwere genotyped: a novel SNP (2390A/G) and 1895C/A (rs12939700). In THRB, a synonymous (735C/T; rs3752874) and an intronic SNP (in9-G/A; rs13063628) were genotyped. No associations between SNPs and thyroid hormone levels (total and free 3,3â²,5-triiodo-L-thyronine [T3] and thyroxine, reverse T3) were found. THRB-in9-G/A was significantly associated with higher serum thyroid stimulating hormone (TSH) (plnTSH 0.01) in the Danish twins, but not in subjects of the Rotterdam Scan Study, although it showed a similar trend.Conclusions:Analysis of the T3 receptor genes revealed 15 SNPs, including 7 novel. Only THRB-in9-G/A was associated with higher serum TSH in a large population of Danish twins.
- Subjects
ISOHORMONES; THYROID hormones; GENE mapping; HORMONE receptors
- Publication
Thyroid, 2008, Vol 18, Issue 10, p1087
- ISSN
1050-7256
- Publication type
Article