title: Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis.
abstract: OBJECTIVE
  The type 2 deiodinase (D2)-Thr92Ala polymorphism has been associated with decreased D2 activity in some in vitro experiments but not in others. So far no association between the D2-Thr92Ala polymorphism and serum thyroid hormone levels has been observed in humans, but in a recent study in athyroid patients, it was suggested that patients homozygous for the Ala(92) allele needed higher T4 doses to achieve TSH suppression. We studied the association between the D2-Thr92Ala polymorphism with thyroid hormone levels and T4 dosage, in patients treated for differentiated thyroid carcinoma (DTC) and in a group of patients treated for Hashimoto thyroiditis.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  We studied 154 patients with DTC treated with TSH suppressive thyroid hormone replacement therapy for longer than 3 years and 141 patients with Hashimoto thyroiditis treated for at least 6 months with T4.
  
  
  METHODS
  In all patients, serum levels of TSH, free T4, T3 and reverse T3 were measured and genotypes of the D2-Thr92Ala polymorphism were determined by Taqman assay. Univariate regression analysis was performed to determine the relation between T4 dosages and the D2-Thr92Ala polymorphism corrected for age, gender, BMI and serum TSH levels.
  
  
  RESULTS
  Both in DTC patients and Hashimoto patients, no association was observed between serum thyroid hormone levels or T4 dosages in presence of the D2-Thr92Ala polymorphism. Categorization of DTC patients according to degree of TSH suppression did not change these results.
  
  
  CONCLUSIONS
  The D2-Thr92Ala polymorphism is not associated with thyroid hormone levels or T4 dose in patients treated for DTC or Hashimoto thyroiditis.
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: K A
authors.initials: KA
authors.lastname: Heemstra
authors.forename: H C
authors.initials: HC
authors.lastname: Hoftijzer
authors.forename: W M
authors.initials: WM
authors.lastname: van der Deure
authors.forename: R P
authors.initials: RP
authors.lastname: Peeters
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.forename: B C
authors.initials: BC
authors.lastname: Appelhof
authors.forename: W M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: E P M
authors.initials: EP
authors.lastname: Corssmit
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.forename: J W A
authors.initials: JW
authors.lastname: Smit
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D050031:Hashimoto Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D013974:Thyroxine; D000097564:Iodothyronine Deiodinase Type II