Replication of association of nine susceptibility loci with Graves' disease in the Chinese Han population

This study is to evaluate the association of 9 single nucleotide polymorphisms (SNPs) with Graves' disease (GD) in different homogenous samples of the Chinese Han population. A total of 2,865 unrelated individuals were enrolled from Linyi City, Shandong Province, China, including 1,139 patients of GD and 1,726 controls. All 9 SNPs showed significant associations with GD (P < 1.3x10(-4), Bonferroni corrected P-c < 0.001). The most significant association was detected at rs2281388 at the HLA-DPB1 locus (P= 1.3x10(-21); OR= 1.62, 95% CI: 1.47-1.79). After adjusting for gender and age, 7 SNPs remained significantly associated with GD (P < 3.4x10(-4), P-c < 0.003). The risk of GD caused by any of these SNPs was not significantly different between female and male participants (P-het > 0.15). Four SNPs located in MHC regions were significantly associated with GD in different ages (P < 8.4x10(-4), P-c < 0.04). The risks of any SNP leading to the development of GD did not differ significantly in different ages (P_trend > 0.02, P-c > 0.18). The rs6457617 at the HLA-DR-DQ locus was significantly correlated with gender in GD patients (P= 0.004, P-c= 0.04). No significant correlation was found between any SNP and age of diagnosis in GD patients (P > 0.02, P-c > 0.17). The 9 previously identified SNPs are associated with GD in the Chinese Han population. And, gender and age may not influence the associations between the 9 SNPs and GD.