甲状腺球蛋白基因外显子33单核苷酸多态性与Graves病停药后复发的相关性分析

Association between single nucleotide polymorphism in exon 33 of thyroglobulin gene and Graves' disease relapse after antithyroid drug withdrawal

目的:探究甲状腺球蛋白基因外显子33单核苷酸多态性(E33SNP)与Graves病(GD)复发的相关性,为临床预测GD抗甲状腺药物(ATD)治疗后的复发提供合理性依据。方法:选取健康对照者232例以及GD治疗后停药的患者243例,且根据GD停药患者的复发情况将观察组分为A、B、C 3个亚组:77例治疗后1年内复发者为A组,86例治疗后1~2年内复发者为B组,80例治疗后2年内未复发者为C组。利用RT-PCR检测对照组和观察组的E33SNP进行分型,对比分析对照组和观察组不同基因型的比率及观察组不同甲状腺球蛋白基因型患者的游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)和促甲状腺激素受体抗体(TRAb)水平,以及眼征、甲状腺肿大程度等临床资料,且对观察组不同基因型患者在治疗后2年内的累积有效率进行对比分析。结果:观察组与对照组E33SNP的基因型差异无统计学显著性,但观察组各个亚组间E33SNP基因型差异具有统计学显著性(P<0.05)。对观察组的A、B、C 3个亚组间不同基因型患者各项甲状腺功能相关指标进行对比分析表明,不同基因型患者的TSH、FT3、FT4水平及甲状腺肿大程度的差异无统计学显著性,而TRAb水平和眼征发生率的差异具有统计学显著性(P<0.05)。此外,E33SNP T/T型GD患者ATD治疗后2年内的累积有效率为61.8%,E33SNP T/C型患者为42.6%,E33SNP C/C型患者为21.3%,差异具有统计学显著性(P<0.05)。结论:E33SNP C/C型GD患者停药后的TRAb水平以及眼征发生率明显偏高,在ATD治疗后更加容易复发,E33SNP T/T型患者则呈现相反的趋势,复发率明显偏低,因此E33SNP C/C型GD患者采用其它治疗方式或者联合治疗方式可能更加合理。

AIM：To explore the association between single nucleotide polymorphism in exon 33（E33SNP）of thyroglobulin gene and Graves’ disease（GD）relapse after antithyroid drug（ATD）withdrawal. METHODS：The healthy controls（232 cases）and GD patients with discontinued treatment（243 cases）were selected. According to the time of relapse,the GD patients were divided into A,B and C subgroups. The A group contained 77 cases of relapse within 1 year,B group contained 86 cases of relapse 1 ~ 2 years after treatment and C group contained 80 cases without recurrence within2 years. The genotypes of E33 SNP were identified by RT-PCR. The genotype ratio of thyroglobulin between control group and observation group was comparatively analyzed,and the levels of thyroid-stimulating hormone（TSH）,free triiodothyronine（FT3）,free thyroxine（FT4）and thyrotropin receptor antibody（TRAb）,ophthalmopathy and goiter size in A,B and C subgroups in different genotype GD patients were investigated. Moreover,cumulative efficiency for patients with different genotypes in the observation group after ATD treatment within 2 years were analyzed. RESULTS：The genotype of E33SNP between observation group and control group had no significant difference,but a significant difference between A,B and C subgroups was observed（P 〈 0. 05）. The levels of TSH,FT3 and FT4,and goiter size of the patients with different genotypes had no significant difference,while the TRAb levels and ophthalmopathy presented a significant difference（P 〈0. 05）. In addition,the cumulative efficiency within 2 years for GD patients with E33 SNP T/T,E33 SNP T/C and E33 SNP C/C genotypes was 61. 8%,42. 6% and 21. 3%,respectively,all with significant differences（P 〈 0. 05）. CONCLUSION：The GD patients with E33 SNP C/C genotype have significantly higher TRAb level and ophthalmopathy rate than those in the patients with E33 SNP C/T and E33 SNP C/C genotypes,and are more likely to relapse after ATD treatment.The GD patients with E33 SNP T/T genotype show a lower recurrence rate. Therefore,combination treatment or other treatment modalities may be more reasonable for the GD patients with E33 SNP C/C genotype.