TSHR基因内含子1区域多态性及其与Graves病的关系

TSHR gene intron I region polymorphism and its relationship with Graves＇ disease

目的探讨中国安徽蚌埠地区汉族人群Graves病患者促甲状腺激素受体（TSHR）基因内含子1上单核苷酸多态性位点（SNP）rsl79247、rsl2101261、rs2284722、rs4903964、rs2300525、rsl7111394与Graves病的关系。方法用TaqMan探针技术，在FluidigmEPl平台上对618例Graves病患者和646名健康对照者进行等位基因分型；同时对Graves病患者检测促甲状腺激素受体抗体（TRAb）水平。结果在6个分析的SNP位点中，除rs2300525外，余5个SNPs均与Graves病易感性关联，以rsl79247-G，rsl2101261-C，rs4903964-G与Graves病相关性最显著（P=2．85x10-10，OR=1．73，95％C／1．46～2．05；P=1．74×10-10，OR=1．73，95％C／1．46～2．05；P=2．24×10-10，OR=1．69，95％C／1．44～1．99）；logistic回归提示rs12101261和rs4903964是TSHR基因内含子1上的主效易感位点。rsl79247-G，rsl2101261-C及rs4903964-G与TRAb阳性Graves病患者显著关联（P=4．24×10-13=5．48×10-13，P=3．89×10-12）。结论TSHR基因内含子1区域rs179247、rs12101261、rs4903964与蚌埠地区汉族人群Graves病明显相关联；并且rs12101261和rs4903964是TSHR基因内含子1上的主效易感位点；TSHR基因可能是TRAb持续阳性Graves病患者的一个主效易感基因。

Objective To investigate the association between the six single nucleotide polymorphisms （SNP） , named as rs179247, rs12101261, rs2284722, rs4903964, rs2300525, rs17111394 in the intron 1 of thyroid stimulating hormone receptor gene （TSHR） and Graves＇ disease （ GD ）. Methods The genotypes of the six SNPs were genotyped by Taqman probe technique on Fluidigm EP1 platform in 618 GD patients and 646 control subjects. Meanwhile, TSH receptor antibodies （TRAb） of the patients were determined. Results Among the six SNPs, five SNPs were strongly associated with GD, with the most signals at rs179247_G, rs 12101261 _C, rM903964 _G （ P = 2.85×10-10, OR = 1.73,95 % CI 1.46-2.05 ; P = 1.74 ×10-10, OR = 1.73,95 % C1 1.46-2.05 ; P = 2.24 ×10-10, OR = 1.69, 95% CI 1.44-1.99 ）. The results of logistic regression analysis indicated that rs12101261 and rs,4903964 were main susceptibility loci of GD in the intron 1 of TSHR. rs179247_G, rs12101261_C, and rs4903964 G were associated with subset of the GD patients with positive TRAb （P = 4.24×10-13 , P = 5.48×10-13 , P = 3.89 ×10-112 ）. Conclusion rs179247, rs12101261, and rs4903964 in TSHR intron 1 were significantly associated with GD in the Chinese Han population from Bengbu city. rs12101261 and rs4903964 were the major susceptibility SNPs associated with GD. TSHR gene may play a main role of susceptibility gene in the subset of GD patients with persistent positive TRAb.