The Role Of Thyroid Stimulating Hormone Receptor Gene D727E Polymorphism In Thyroid Benign And Malignant Tumors

Background and Objective: Thyroid nodules rarely occur under low thyroid stimulating hormone(TSH)levels.Thyroid stimulating hormone receptor(TSHR)gene is one of the important candidate genes in the pathogenesis of thyroid diseases.This article explored the distribution of the TSHR gene codon 727 polymorphism(p.Asp727 Glu,p.D727E)in patients with benign or malignant thyroid tumors under low TSH.Methods: A total of 1256 patients with thyroid nodules were admitted to the Department of Breast-Thyroid-Vascular Surgery in the South Campus of Shanghai General Hospital,affiliated to Shanghai Jiao Tong University,from January 2018 to December 2019.Among them,37 patients had TSH levels below the normal range,17 patients were diagnosed as nodular goiter(NG),and 20 patients were diagnosed as differentiated thyroid carcinoma(DTC).In addition,10 patients with NG or DTC under normal TSH level during the same period were randomly selected as a control study.DNA from tissue sections of all 57 patients was extracted,and whole exome sequencing of TSHR gene was performed.Statistical analysis of the relationship between the TSHR D727 E and clinical data.Results: The TSHR D727 E GC+GG genotype accounted for 37.0% of NG patients and 33.3% of DTC,and the distribution was similar.Subgroup analysis showed that the incidence of GC+GG genotype in NG patients with low TSH status(9/17,52.9%)was significantly higher than that of normal TSH subgroup(1/10,10%)(p=0.042),but this This phenomenon was not found in DTC patients(35.0% vs 30.0%,p=1).For NG patients with low TSH level,the GC+GG genotype might have a larger age(56.000 vs 42.000 years,p=0.059)and smaller lesions size(2.400 vs 4.000 cm,p=0.114)than CC genotype and this trend was not seen under normal TSH levels.The same trend existed in patients with DTC.In addition,compared with the normal TSH subgroup,the GC type patients in the low TSH subgroup showed a lower rate of metastasis,while the CC type had similar metastasis between the two subgroups.Moreover,47.4%(9/19)of female DTC patients had GC genotype,which was significantly higher than the 16% of Asian population with GC genotype,while the proportion of male DTC patients with GC type(1/11,9.09%)was Close.In NG patients,contrary to DTC,men were more likely to have the GC+GG genotype(5/7 vs 5/20,p=0.029).Conclusions: TSHR D727 E GC+GG genotype might be related to the occurrence of NG under low TSH,but there was no obvious correlation in the occurrence of DTC.In the low TSH state,the GC+GG genotype might have a protective effect on the progression of NG and DTC.DTC patients with CC genotype might be insensitive to the effects of low TSH.In addition,the GC+GG genotype showed different gender advantages in benign and malignant thyroid diseases.Women were more likely to develop DTC,while men were more likely to develop NG.