The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins

Wendy M van der Deure; Pia Skov Hansen; Robin P Peeters; André G Uitterlinden; Mogens Fenger; Kirsten Ohm Kyvik; Laszlo Hegedüs; Theo J Visser

doi:http://dx.doi.org/10.1111/j.1365-2265.2008.03420.x

The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins

Wendy M van der Deure, Pia Skov Hansen, Robin P Peeters, André G Uitterlinden, Mogens Fenger, Kirsten Ohm Kyvik, Laszlo Hegedüs, Theo J Visser

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

28 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Sep-11

Originalsprog	Engelsk
Tidsskrift	Clinical Endocrinology
Vol/bind	70
Udgave nummer	6
Sider (fra-til)	954-60
ISSN	0300-0664
DOI	https://doi.org/10.1111/j.1365-2265.2008.03420.x
Status	Udgivet - 2009

Adgang til dokumentet

http://dx.doi.org/10.1111/j.1365-2265.2008.03420.x

Citationsformater

van der Deure, W. M., Hansen, P. S., Peeters, R. P., Uitterlinden, A. G., Fenger, M., Kyvik, K. O., Hegedüs, L., & Visser, T. J. (2009). The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins. Clinical Endocrinology, 70(6), 954-60. https://doi.org/10.1111/j.1365-2265.2008.03420.x

The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins. / van der Deure, Wendy M; Hansen, Pia Skov; Peeters, Robin P; Uitterlinden, André G; Fenger, Mogens; Kyvik, Kirsten Ohm; Hegedüs, Laszlo; Visser, Theo J.

I: Clinical Endocrinology, Bind 70, Nr. 6, 2009, s. 954-60.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

van der Deure, WM, Hansen, PS, Peeters, RP, Uitterlinden, AG, Fenger, M, Kyvik, KO, Hegedüs, L & Visser, TJ 2009, 'The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins', Clinical Endocrinology, bind 70, nr. 6, s. 954-60. https://doi.org/10.1111/j.1365-2265.2008.03420.x

van der Deure, Wendy M ; Hansen, Pia Skov ; Peeters, Robin P ; Uitterlinden, André G ; Fenger, Mogens ; Kyvik, Kirsten Ohm ; Hegedüs, Laszlo ; Visser, Theo J. / The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins. I: Clinical Endocrinology. 2009 ; Bind 70, Nr. 6. s. 954-60.

@article{2c842e848e4a4739a016d06378533a8c,

title = "The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins",

abstract = "Introduction: Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3' untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels. Objective: In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analyzed the underlying functional mechanism by performing mRNA stability measurements and analyzed the effect of these variants on D1 activity. Methods: Serum thyroid measurements and genotypes of the D1-C785T and D1-A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1-transfected JEG3 cells. Results: Carriers of the D1-785T allele had 3.8% higher FT4 and 14.3 % higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0.87% and 1.79%, respectively, of the variation in serum FT4 and rT3. The D1-A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild-type D1 and the 2 variants. Conclusion: The D1-C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated.",

author = "{van der Deure}, {Wendy M} and Hansen, {Pia Skov} and Peeters, {Robin P} and Uitterlinden, {Andr{\'e} G} and Mogens Fenger and Kyvik, {Kirsten Ohm} and Laszlo Heged{\"u}s and Visser, {Theo J}",

year = "2009",

doi = "http://dx.doi.org/10.1111/j.1365-2265.2008.03420.x",

language = "English",

volume = "70",

pages = "954--60",

journal = "Clinical Endocrinology",

issn = "0300-0664",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - The effect of genetic variation in the type 1 deiodinase gene on the inter-individual variation in serum thyroid hormone levels. An investigation in healthy Danish twins

AU - van der Deure, Wendy M

AU - Hansen, Pia Skov

AU - Peeters, Robin P

AU - Uitterlinden, André G

AU - Fenger, Mogens

AU - Kyvik, Kirsten Ohm

AU - Hegedüs, Laszlo

AU - Visser, Theo J

PY - 2009

Y1 - 2009

N2 - Introduction: Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3' untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels. Objective: In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analyzed the underlying functional mechanism by performing mRNA stability measurements and analyzed the effect of these variants on D1 activity. Methods: Serum thyroid measurements and genotypes of the D1-C785T and D1-A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1-transfected JEG3 cells. Results: Carriers of the D1-785T allele had 3.8% higher FT4 and 14.3 % higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0.87% and 1.79%, respectively, of the variation in serum FT4 and rT3. The D1-A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild-type D1 and the 2 variants. Conclusion: The D1-C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated.

AB - Introduction: Genetic factors have a considerable influence on serum thyroid hormone levels. The C785T and A1814G polymorphisms, located in the 3' untranslated region of the type 1 deiodinase (D1) gene have been associated with serum FT4 and rT3 levels. Objective: In healthy Danish twins, we examined the association of these polymorphisms with serum thyroid hormone levels and determined the proportion of genetic influence explained by these variants. We analyzed the underlying functional mechanism by performing mRNA stability measurements and analyzed the effect of these variants on D1 activity. Methods: Serum thyroid measurements and genotypes of the D1-C785T and D1-A1814G polymorphisms were determined in 1192 twins. Structural equation modelling was used to determine heritability estimates. Functional analyses were carried out in D1-transfected JEG3 cells. Results: Carriers of the D1-785T allele had 3.8% higher FT4 and 14.3 % higher rT3 levels, resulting in a lower T3/T4 and T3/rT3 ratio and a higher rT3/T4 ratio. This polymorphism explained 0.87% and 1.79%, respectively, of the variation in serum FT4 and rT3. The D1-A1814G polymorphism was not associated with serum thyroid hormone levels. No differences in D1 mRNA decay rate or D1 activity were observed between wild-type D1 and the 2 variants. Conclusion: The D1-C785T polymorphism is consistently and significantly associated with serum thyroid hormone levels. However, the proportion of genetic influence explained by this particular polymorphism is small. No effect of the polymorphism on D1 mRNA decay rate or D1 activity was observed. The underlying functional mechanism needs to be elucidated.

U2 - http://dx.doi.org/10.1111/j.1365-2265.2008.03420.x

DO - http://dx.doi.org/10.1111/j.1365-2265.2008.03420.x

M3 - Journal article

VL - 70

SP - 954

EP - 960

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 6

ER -