Lack of association of nonautoimmune hyperfunctioning thyroid disorders and a germline polymorphism of codon 727 of the human thyrotropin receptor in a European Caucasian population.

Constitutively activating mutations of the human TSH receptor (hTSHR) gene have been implicated as a major cause of hyperfunctioning nonautoimmune thyroid disease. However, significant geographic differences in the prevalence of these mutations have been observed. Recently, a high frequency of a germline polymorphism at codon 727 of the cytoplasmic tail of the hTSHR has been demonstrated in patients with toxic multinodular goiter. In the present study we assessed whether the codon 727 polymorphism is associated with hyperfunctioning thyroid adenomas. PCR followed by restriction enzyme digestion were used to genotype a total of 128 European Caucasian patients with toxic nonautoimmune thyroid disease (83 with toxic adenoma, 31 with toxic multinodular goiter, and 14 with disseminated autonomy) and to compare their codon 727 polymorphism frequencies with those of 99 healthy controls and 108 patients with Graves’ disease. All individuals were drawn from an identical ethnic background. Sequencing of PCR product...