中文摘要：

目的 研究促甲状腺素受体（TSHR）基因与山东沿海地区汉族人群Graves病（GD）易感性之间的关系。方法 选取山东沿海地区471例汉族GD患者和472例健康体检者为研究对象，应用TaqMan探针技术，在Fluidigm EP1平台上对TSHR基因第一内含子区6个标签SNP位点进行分型检测，并构建单体型。结果 rs179247、rs12101261、rs4903964和rs17111394等位基因频率在GD组和对照组中有显著性差异（P=0.004、P=0.001、P=0.005、P=0.012）。rs179247-A、rs4903964-A和rs17111394-C等位基因携带者发生GD的风险分别增加34%（OR=1.34，95%CI 1.10～1.63）、30%（OR=1.30，95%CI 1.08～1.57）和31%（OR=1.31，95%CI 1.06～1.62）。与对照组相比，GD组rs12101261-C等位基因频率显著降低（36.0%对28.9%，P=0.001），rs12101261-C等位基因携带者发生GD的风险降低28%（OR=0.72，95%CI 0.60～0.88）。Logistic回归分析显示，rs12101261是GD发病的一个独立的易感位点（P=0.033）。单体型分析发现，G-G-C-G-T-T单体型频率在对照组明显高于GD组，差异有统计学意义（P=0.017，OR=0.762，95%CI 0.609～0.953），而A-G-T-A-C-C单体型频率在GD组明显高于对照组（P=0.033），该单体型发生GD的风险增加63%（OR=1.630，95%CI 1.035～2.567）。结论 TSHR基因多态性及单体型与山东沿海地区汉族人GD的发生相关，rs12101261是独立易感位点。

英文摘要：

Objective To investigate the association of thyroid stimulating hormone receptor（TSHR） gene polymorphisms and haplotypes with Graves′ disease （GD） in Han population from coastal areas in Shandong province. Methods Four hundred and seventy-one GD patients and 472 controls from coastal areas in Shandong province were enrolled for genotyping 6 single nucleotide polymorphisms （SNPs） in TSHR gene by TaqMan probe technique on Fluidigm EPl platform. Haplotypes and their frequencies were established and analyzed by SHEsis online software. Results A significant difference in allele frequencies of rs179247, rs12101261, rs4903964, and rs17111394 was found between the GD patients and the controls（P=0.004, P=0.001, P=0.005, and P=0.012）. GD risk in individuals carrying rs179247-A, rs4903964-A, and rs17111394-C alleles was increased by 34%, 30%, and 31%, respectively. The allele C frequency of rs12101261 was significantly lower in GD than that in controls with an odds ratio of 0.72（36.0% vs 28.9%, P=0.001）. Logistic regression identified that rs12101261 was an independent susceptibility locus of GD. The frequency of the A-G-T-A-C-C haplotype in GD patient group was higher than that in control group （P=0.033） with an odds ratio of 1.630, while the G-G-C-G-T-T haplotype was strongly protective（P=0.017, OR=0.762, 95%CI 0.609-0.953）. Conclusion TSHR gene polymorphisms and haplotypes are associated with GD in Han population from coastal areas in Shandong province, and rs12101261 may contribute a risk of GD independently.