title: The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark. piaskovhansen@dadlnet.dk
authors.forename: Pia Skov
authors.initials: PS
authors.lastname: Hansen
authors.forename: Wendy M
authors.initials: WM
authors.lastname: van der Deure
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.forename: Ivan
authors.initials: I
authors.lastname: Iachine
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Kirsten O
authors.initials: KO
authors.lastname: Kyvik
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D019655:Quantitative Trait, Heritable; D011989:Receptors, Thyrotropin / Q000235:genetics*; D012044:Regression Analysis; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000276:immunology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood*
chemical_list: D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D013972:Thyrotropin