甲状腺球蛋白基因多态性与自身免疫性甲状腺病的相关性_医学论文.docVIP

甲状腺球蛋白基因多态性与自身免疫性甲状腺病的相关性_医学论文 甲状腺球蛋白基因多态性与自身免疫性甲状腺病的相关性_医学论文 作者：张进安，买尔哈巴，于志云，肖婉霞，王宇 【关键词】 自身免疫性甲状腺疾病,,Graves病,,桥本氏甲状腺炎,,甲状腺球蛋白；单核苷酸多态性 【Abstract】 AIM: To identify the presence of previously reported thyroglobulin (Tg) gene singlenucleotide polymorphism (SNP) in Chinese people and to investigate their potential relation to the aetiology of autoimmune thyroid disease (AITD). METHODS: In 228 patients with AITD ［146 with Greaves disease (GD) and 82 with Hashimotos thyroiditis (HT)］ and 131 normal Chinese subjects, PCRRFLP was used to determine the SNPs of exon 10, 12 and 33. RESULTS: Four reported exonic SNPs of Tg genes E10SNP24 T/G, E10SNP158 T/C, E12SNP A/G and E33SNP C/T were confirmed in Chinese population. No differences in allele and genotype frequencies of four SNPs were observed between AITD cases and controls or when GD or HT was analyzed alone. Strong linkage disequilibrium (LD) between E10SNP24 and E10SNP158 (D′=0.96) and a weak LD between E12SNP with E10SNP24 and E10SNP158 (D′=0.73, D′=0.74, respectively) were found. Furthermore, the combination of C allele of the exon 33 with three SNPs of exon1012 cluster (AGC) was found to be associated with HT (OR=3.06, 0.01). CONCLUSION: This study not only confirmed the common Tg gene variants in Chinese people, but also demonstrated that some SNPs within Tg gene played a causal role for HT. 【Keywords】 AITD GD HT thyroglobulin SNP 【摘要】 目的: 检测中国人甲状腺球蛋白（Tg）基因的外显子10,12,33是否存在单核苷酸多态性(SNP)，研究其与自身免疫性甲状腺疾病（AITD）的关系. 方法: 对228例AITD患者［其中Greaves病（GD）146例，桥本甲状腺炎（HT）82例］和131例健康对照者采用PCRRFLP方法检测Tg基因外显子10,12和33的SNPs. 结果: ①Tg基因存在E10SNP24 T/G, E10SNP158 T/C，分别为E12SNP A/G和E33SNP C/T多态性位点. ②四个位点基因型及等位基因频率在AITD组或GD亚组或HT亚组与正常对照组之间差异无统计学意义(Pgt0.05). ③E10SNP24与E10SNP158，E12SNP与E10SNP24, E12SNP与E10SNP158之间存在连锁不平衡，D′值分别为0.96, 0.73和0.74. ④HT患者的E33SNP为C等位基因时，E12SNP A，E10SNP24 G和E10SNP158 C在同一染色单体的基因频率显著多于对照组（0.01, OR=3.06）. 结论：中国北方汉族人存在Tg基因外显子10,12和33的单核苷酸多态性（SNP），且证实Tg基因与此类人群HT的发病有关. 【关键词】 自身免疫性甲状腺疾病 Graves病 桥本氏甲状腺炎 甲状腺球蛋白；单核苷酸多态性 0引言 G