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 products was used to confirm the mutation analysis. We found no significant differences in codon 727 polymorphism frequencies between patients with autonomously functioning thyroid disorders (13. 3%) and the healthy control group (16. 2%; P = 0 VSports手机版. 57). Moreover, the subtypes of toxic nonautoimmune thyroid disease (toxic adenoma, 13. 2%; multinodular goiter, 9. 6%; disseminated autonomy, 21. 4%) were not related to significant differences in codon 727 polymorphism frequencies compared with the healthy control group (P = 0. 67, P = 0. 40, and P = 0. 70, respectively). Additionally, there were no significant differences between patients with Graves' disease (21. 3%) and healthy controls (P = 0. 38). In conclusion, our data do not support an association between the codon 727 polymorphism of the hTSHR and toxic thyroid adenomas or toxic multinodular goiter in our study population. Thus, the codon 727 polymorphism of the hTSHR does not appear to be involved in the evolution of autoimmune or nonautoimmune hyperthyroidism in the European Caucasian population. .