Genetic study in a large cohort supported different pathogenesis of Graves' diseases and Hashimoto's hypothyroidism.

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the two main autoimmune thyroid diseases with both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these two closely related diseases. OBJECTS&DESIGN: In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2,682 patients with HT, 4,980 patients with GD and 3,892 controls, The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS with the logistic regression analysis adjusted for sex and age. RESULTS: we identified 11 susceptibility loci for HT in the Chinese Han population, with four loci including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in MHC-IB region and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5x10-8. Five loci were reported to be associated with HT for the first time. We also identified six susceptibility loci with heterogeneity between GD and HT. Out of them, four loci were associated with GD, but not with HT including HLA-DPB1, CD40, TSHR and TG, and the association of HLA-B with GD was stronger than that with HT but the association of SLAMF6 was reversed. CONCLUSION: Our findings suggested that the pathogenesis of HT and GD was different.