Association Of Thyroglobulin Gene Exon 33 Single Nucleotide Polymorphism With The Relapse Of Graves' Disease After Antithyroid Drug Withdrawal

Objective: Genetics factors played an important role in the pathogenesise of Graves' disease(GD).Antithyroid drug(ATD)was still the major method for the treatment of GD till today.However,the relapsing rate of GD after drug withdrawal was higher.Maybe there was a relationship between genetic factors and relapse of GD after drug withdrawal till today.The objective of the present study was to analyze the relationship between the polymorphism of exon 33 of thyroglobulin gene(E33SNP)and the relapse of Graves' disease after antithyroid drug withdrawal,according to the outcome of the recurrence or not of GD.Methods: A total of 108 patients with Graves' disease in our clinic of endocrinology were selected and enrolled in our study from September 2015 to December 2016,according to the chronological order.The clinical data were collected and analyzed retrospectively.According to the recurrence or not of Graves' disease after the withdrawal,three different groups were divided as following:1)A group: will be discontinued within 1 year after the recurrence of Graves' disease,38 patients;2)B group: 1 to 2 years after the withdrawal of Graves' disease recurrence,37patients;3)C group:2 years after the withdrawal of Graves' disease has not been relapsed,33 patients.At the same time,the other included in our hospital physical examination center to exclude Graves' disease examination of a total of 33 cases as a control group.The genotypes of E33 SNP were identified by PCR-RFLP.All subjects were genotyped and determined thyroid function(FT3,FT4,TSH,Tg,TRAb)by chemiluminescence immunoassay.The genotype frequency,the frequency of allele and the thyroid function(FT3,FT4,TSH,Tg,TRAb)of different genotype Graves' patients were compared and analyzed.Results: There was no different of the frequency of genetype and allele between GD and control group.Compare the frequency of genetype and allele,index of thyroid function in different genetype patients: the composition of CC genetype patients was 78.95 %(30/38)in the A group,which was significantly higher than that in the B group56.76%(21/37)and C group 33.33%(11/33)(P <0.05);and the ratio of CT genetype patients was 10.53%(4/38),which was significantly lower than that in the B group 29.73%(11/37)and C group 39.39%(13/33)(P<0.05).The proportion of CC genetype patients in the B group was 56.76%(21/37),which was significantly higher than that in the C group 33.33%(11/33)(P<0.05).respectively,which were significantly higher thyrotropin receptor antibody(TRAb)level in the CC genetype group than in the other genetype groups(P <0.05).Conclusion: There was a relationship between the polymorphism of exon 33 of thyroglobulin gene and the relapse of Graves' disease after antithyroid drug withdrawal;The E33 SNP CC genotype GD patients have a significantly higher TRAb level after ATD treatment,which were more likely to relapse.Should be prolonged low dose maintenance time for antithyroid drugs in clinical treatment,in order to reduce the recurrence rate of Graves' disease after antithyroid drug withdrawal.