TSHR Gene Intron1Region Polymorphism And Its Elationship With Graves’ Disease

Objective: To investigate the allele and genotype descriptions of single neucleotide polymorphisms （SNPs） thyroid stimulating hormone receptor gene （TSHR） intron1inchromosome14between Graves’ disease （GD） and China Han population from Bengbucity, Anhui province. To identify the association between polymorphisms of thyroidstimulating hormone receptor gene intron1at positions rs179247, rs12101261，rs2284722，rs4903964，rs2300525，rs17111394and Graves’ disease （GD）. To discussthe associations with many clinical manifestations of the GD patients including serumconcentration of thyroid stimulating hormone receptor antibody（TRAb）, sex, thyroiddiffused goiter, ophthalmic signs, relapse and family history. Methods: The genotypesof the six SNPs were genotyped by Taqman probe technique on Fluidigm EP1platformin618GD patients and646control subjects recruited from Bengbu city, Anhuiprovince and make linkage analysis and correlation analysis with them. Meanwhile,TSH receptor antibodies （TRAb） of the patients were measured. Results: Among thesix SNPs, five SNPs were strongly associated with GD in the Chinese Han population,with the most signals at rs179247_G, rs12101261_C, rs4903964_G (P=2.85×10^-10，OR=1.73，95%CI：1.46-2.05； P=1.74×10^-10，OR=1.73，95%CI：1.46-2.05；P=2.24×10^-10，OR=1.69，95%CI：1.44-1.99). The results of logistic regression analysisindicated that rs12101261, rs4903964were main susceptibility locus of GD in the intron1of TSHR. Furthermore, no other clinical features except serum TRAb concentrationshowed significant difference （P=0.0045, P=0.0096） among three subgroups （CC, CT,TT） of rs12101261with positive rate at6.00%,35.25%,58.75%and three subgroups（GG,AG,AA） of rs4903964with positive rate at7.48%、41.65%、50.87%,respectively.In patients with positive TRAb levels, rs12101261_C, rs4903964_G were stronglyassociated with GD （P=5.48×10-13，OR=0.4859; P=3.89×10-12，OR=0.5104）; however,the association were obviously weaker in patients with negative serum TRAb levels （P=0.0994，OR=0.79; P=0.0591，OR=0.7693）. rs2284722was strongly associated withGD who have family history（P=8.2×10-5，OR=2.24,95%CI=2.49-3.37）. Conclusion： rs179247, rs12101261, rs4903964in TSHR intron1were the most significantlyassociated with GD in the Chinese Han population from Bengbu city. rs12101261,rs4903964were the major susceptibility SNPs associated with GD and the polymorphisms was associated with the production of TRAb but not with the serum concentrationof thyroid stimulating hormone receptor antibody（TRAb）, sex, thyroid diffused goiter,ophthalmic signs, relapse.TSHR gene may be a main effect of susceptibility gene insubset of TRAb persistent positive GD patients.