The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

P.S. Hansen; W.M. van der Deure; R.P. Peeters; I. Iachine; Mogens Fenger; T.I.A. Sørensen; K.O. Kyvik; T.J. Visser; L. Hegedus; Pia Skov Hansen; Wendy M van der Deure; Robin P Peeters; Ivan Iachine; Mogens Fenger; Thorkild I A Sørensen; Kirsten O Kyvik; Theo J Visser; Laszlo Hegedüs

doi:http://dx.doi.org/10.1111/j.1365-2265.2007.02820.x

The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

P.S. Hansen, W.M. van der Deure, R.P. Peeters, I. Iachine, Mogens Fenger, T.I.A. Sørensen, K.O. Kyvik, T.J. Visser, L. Hegedus, Pia Skov Hansen, Wendy M van der Deure, Robin P Peeters, Ivan Iachine, Mogens Fenger, Thorkild I A Sørensen, Kirsten O Kyvik, Theo J Visser, Laszlo Hegedüs

38 Citationer (Scopus)

Abstract

OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. MEASUREMENTS: The effect of the genotype on the traits (mean +/- SD) was established; associations between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted for 0.91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0.001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68.2% to 67.8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels. CONCLUSIONS: The TSHR-727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid-related measures.
Udgivelsesdato: 2007-Jun

Originalsprog	Engelsk
Tidsskrift	Clinical Endocrinology
Vol/bind	66
Udgave nummer	6
Sider (fra-til)	827-32
Antal sider	5
ISSN	0300-0664
DOI	https://doi.org/10.1111/j.1365-2265.2007.02820.x
Status	Udgivet - 2007

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http://dx.doi.org/10.1111/j.1365-2265.2007.02820.x

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Hansen, P. S., Deure, W. M. V. D., Peeters, R. P., Iachine, I., Fenger, M., Sørensen, T. I. A., Kyvik, K. O., Visser, T. J., Hegedus, L., Hansen, P. S., van der Deure, W. M., Peeters, R. P., Iachine, I., Fenger, M., Sørensen, T. I. A., Kyvik, K. O., Visser, T. J., & Hegedüs, L. (2007). The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population. Clinical Endocrinology, 66(6), 827-32. https://doi.org/10.1111/j.1365-2265.2007.02820.x

Hansen, PS, Deure, WMVD, Peeters, RP, Iachine, I, Fenger, M, Sørensen, TIA, Kyvik, KO, Visser, TJ, Hegedus, L, Hansen, PS, van der Deure, WM, Peeters, RP, Iachine, I, Fenger, M, Sørensen, TIA, Kyvik, KO, Visser, TJ & Hegedüs, L 2007, 'The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population', Clinical Endocrinology, bind 66, nr. 6, s. 827-32. https://doi.org/10.1111/j.1365-2265.2007.02820.x

@article{22db971020ec11ddbc23000ea68e967b,

title = "The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population",

abstract = "OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. MEASUREMENTS: The effect of the genotype on the traits (mean +/- SD) was established; associations between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted for 0.91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0.001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68.2% to 67.8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels. CONCLUSIONS: The TSHR-727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid-related measures.",

author = "P.S. Hansen and Deure, {W.M. van der} and R.P. Peeters and I. Iachine and Mogens Fenger and T.I.A. S{\o}rensen and K.O. Kyvik and T.J. Visser and L. Hegedus and Hansen, {Pia Skov} and {van der Deure}, {Wendy M} and Peeters, {Robin P} and Ivan Iachine and Mogens Fenger and S{\o}rensen, {Thorkild I A} and Kyvik, {Kirsten O} and Visser, {Theo J} and Laszlo Heged{\"u}s",

year = "2007",

doi = "http://dx.doi.org/10.1111/j.1365-2265.2007.02820.x",

language = "English",

volume = "66",

pages = "827--32",

journal = "Clinical Endocrinology",

issn = "0300-0664",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

AU - Hansen, P.S.

AU - Deure, W.M. van der

AU - Peeters, R.P.

AU - Iachine, I.

AU - Fenger, Mogens

AU - Sørensen, T.I.A.

AU - Kyvik, K.O.

AU - Visser, T.J.

AU - Hegedus, L.

AU - Hansen, Pia Skov

AU - van der Deure, Wendy M

AU - Peeters, Robin P

AU - Iachine, Ivan

AU - Fenger, Mogens

AU - Sørensen, Thorkild I A

AU - Kyvik, Kirsten O

AU - Visser, Theo J

AU - Hegedüs, Laszlo

PY - 2007

Y1 - 2007

N2 - OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. MEASUREMENTS: The effect of the genotype on the traits (mean +/- SD) was established; associations between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted for 0.91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0.001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68.2% to 67.8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels. CONCLUSIONS: The TSHR-727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid-related measures.

AB - OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. MEASUREMENTS: The effect of the genotype on the traits (mean +/- SD) was established; associations between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted for 0.91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0.001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68.2% to 67.8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels. CONCLUSIONS: The TSHR-727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid-related measures.

U2 - http://dx.doi.org/10.1111/j.1365-2265.2007.02820.x

DO - http://dx.doi.org/10.1111/j.1365-2265.2007.02820.x

M3 - Journal article

SN - 0300-0664

VL - 66

SP - 827

EP - 832

JO - Clinical Endocrinology

JF - Clinical Endocrinology

IS - 6

ER -

The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

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