The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population
The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population
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DOI：
10.1111/j.1365-2265.2007.02820.x
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发表时间：
2007-06-01
影响因子：
3.2
通讯作者：
Hegedus, Laszlo
中科院分区：
文献类型：
--
作者：
Hansen, Pia Skov;van der Deure, Wendy M.;Hegedus, Laszlo
目的TSH受体（TSH receptor，TSHR）基因Asp 727 Glu多态性与血清TSH水平相关。然而，这种多态性占遗传变异的比例是未知的。在本研究中，我们（1）检测了Asp 727 Glu多态性与1241名健康丹麦双胞胎个体的甲状腺大小、血清TSH水平、甲状腺激素和甲状腺抗体的关系，（2）评估了该多态性对性状变异和遗传方差的贡献。（平均值+/- SD）;评估TSHR-Asp 727 Glu多态性与甲状腺稳态测量之间的关联，并通过将基因型信息纳入结构方程模型来量化多态性对性状表型变异的影响。Asp 84.9%，Asp/Glu 14.5%，Glu/Glu 0.6%。TSHR-Glu 727等位基因携带者的TSH水平较低（非携带者与携带者：1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l，P = 0.04）。回归分析显示TSHR-Asp 727 Glu多态性与血清TSH水平相关（P = 0.007）。该多态性解释了血清TSH水平总表型变异的0.91%。在定量遗传建模中包括基因型改善了模型拟合（P = 0.001）;然而，对血清TSH的遗传影响不归因于这种特定的遗传变异，仅从68.2%降低到67.8%。该多态性与甲状腺大小、甲状腺激素水平和甲状腺抗体水平无显著相关性。结论TSHR-727 Glu等位基因与TSH水平降低相关，但对遗传变异的贡献很小。未发现与其他甲状腺相关指标相关。
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.Meassurements 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.