The Study On Mutations Of The Extracellular Domain Of Human Thyrotropin Receptor Gene In The Patients With Thyroid Diseases

The human TSH(thyrotropin) receptor (hTSHR) exists in the plasma membrane of the thyrocyte and plays a critical role in thyroid function and growth. The extracellular domain of the receptor, which is responsible for ligand binding, is thought to be the central autoantigen in Graves' disease and some other autoimmune thyroid disease (AITD). Autoantibodies (TSHRAb) against the TSHR are thought to be involved in the expression of AITD. The gene mutations of the TSHR are thought to be the main causes of the thyroid autonomous hyperfunctioning adenomas and hyperfunctioning nodules, as well as the causes of some nonautoimmune hyper- of hypothyroidism. Mutations of the extracellular domain of the TSHR gene are suspected to participate in the etiology fo the AITD. In this research, total RNAs were extracted from the thyroid tissues of four normal controls, twelve Graves' disease, four Hashimoto' thyroiditis and eleven nodular goiters patients. The extracellular domain of TSHR gene were amplified by reverse transcription梡olymerase chain reaction (RT-PCR) and were sequenced with CEQ 2000 Genetic Analyzer. The results showed that the methods of this experience were correct. The normal controls and the thyroid disease patients had the same gene sequences of the extracellular-3-domain of TSHR. No mutation was found, except for a silent base exchange in exon 7 (Asn187) 661 base, in which 20 samples were "T, 11 samples were "C", without change of amino acid of the TSHR. This study did not reveal TSH receptor mutations in the extracellular domain of TSHR. Other molecular pathogenetic mechanisms may be involved and more researchs are demanded.