摘要目的 探讨促甲状腺激素受体(TSHR)基因rs2268458位点单核苷酸多态性与Graves病(GD)和桥本甲状腺炎(HT)的关联性.方法 2016年河北省选取沧州市居民甲状腺疾病流行病学调查项目确诊的部分GD和HT患者为病例组,根据临床诊断不同分为GD组和HT组,同时选取当地性别、年龄与病例组相近的健康人群作为对照组.所有研究对象均来自汉族,彼此无亲缘关系.采用限制片段内切酶法(RFLP)检测所有研究对象TSHR基因rs2268458 (C/T)的基因型和等位基因,分析患病风险(比值比,OR)和95％可信区间(95％CI).结果 GD组87例,年龄为(43.17±12.56)岁,其中女性64例、男性23例.HT组31例,年龄为(44.41±16.51)岁,其中女性26例、男性5例.对照组147例,年龄为(40.26±9.31)岁,其中女性80例、男性67例.对各组研究对象进行Hardy-Weinberg平衡检验,结果显示P均＞0.05,提示研究样本具有群体代表性.基因分析结果显示,在女性中,GD组的C等位基因频率显著高于对照组[x2=4.632,36.7％(47/128)比25.0％(40/160),P＜ 0.05,OR=1.741,95％CI=1.048～2.891],GD组与对照组间各基因型(CC、CT、TT)频率分布比较差异有统计学意义(x2=6.104,P＜0.05),且GD患者中TC+CC联合基因型频率显著高于对照组(x2=6.092,P＜ 0.05,OR=2.333,95％CI=1.184～4.598);HT组与对照组的基因型(CC、CT、TT)频率分布和等位基因频率间比较差异无统计学意义(P均＞ 0.05).在男性中,各组间的基因型(CC、CT、TT)频率分布和等位基因频率间比较差异无统计学意义(P均＞ 0.05).结论 在沧州地区的女性中,TSHR基因的rs2268458位点单核苷酸多态性与GD的易感性有关,但未发现与HT有关,并且C基因型以显性遗传方式增加GD的患病风险.

abstractsObjective To investigate the association of single nucleotide polymorphisms in the rs2268458 locus of thyroid-stimulating hormone receptor (TSHR) gene with Graves disease (GD) and Hashimoto's thyroiditis (HT).Methods Part of the cases diagnosed through the epidemiological investigation project about thyroid diseases of Cangzhou City in 2016 was selected as the case group.The case group was subdivided into GD group and HT group according to the diagnosis.At the same time,healthy people with similar gender and age to the case group were selected as the control group.All subjects were from the Han nationality and were not related to each other.The genotypes and alleles of the TSHR gene rs2268458 (C/T) of all subjects were detected by restriction endonuclease (RFLP).And based on genotyping analysis of patient risk (odds ratio,OR) and 95％ confidence interval (95％CI).Results There were 87 cases in GD group [aged (43.17 ± 12.56) years old],including 64 females and 23 males.There were 31 cases in HT group [aged (44.41 ± 16.51) years old],including 26 females and 5 males.In the control group,there were 147 cases [age (40.26 ± 9.31) years old],including 80 females and 67 males.HardyWeinberg equilibrium test was performed on each group.The results showed that P ＞ 0.05,suggesting that the study samples were representative of the population.The results of genetic analysis showed that in females,the C allele frequency of GD patients was significantly higher than that of the control group [x2 =4.632,36.7％ (47/128) vs 25.0％ (40/160),P ＜ 0.05,OR =1.741,95％CI =1.048-2.891].The frequency distribution of each genotype (CC,CT,TT) at TSHR rs2268458 (T/C) was statistically different (x2 =6.104,P ＜ 0.05),and the frequency of TC ± CC combined genotype was significantly higher in GD patients than in controls (x2 =6.092,P ＜ 0.05,OR =2.333,95％ CI =1.184-4.598),however,there was no statistical difference between the HT group and the control group in genotype (CC,CT,TT) frequency distribution and alleles (P ＞ 0.05).In males,there was no statistically significant difference in genotype (CC,CT,TT) frequency distribution and allele between groups (P ＞ 0.05).Conclusion Among women in Cangzhou,the single nucleotide polymorphism of rs2268458 in TSHR gene is associated with the susceptibility to GD,but not to HT,and C genotype increases the risk of GD by dominant inheritance.