The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves' disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles.
We applied HLA imputation to genome-wide association study (GWAS) data for Graves' disease in Japanese (n = 9,003) and found that amino acid polymorphisms of multiple class I and class II HLA genes independently contribute to disease risk (HLA-DPB1, HLA-A, HLA-B and HLA-DRB1; P < 2.3 × 10(-6)), with the strongest impact at HLA-DPB1 (P = 1.6 × 10(-42)).
In contrast, HLA components on 3 common haplotypes in Japanese showed significant protective effects against the development of GD and HT (HLA-A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01 and HLA-A*24:02-C*07:02-B*07:02-DRB1*01:01-DQB1*05:01-DPB1*04:02 haplotypes for GD and HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype for GD and HT).
The results suggested that SNPs at PRR3 and ABCF1 genes and the haplotype composed by SNPs at GNL1 and PRR3 between the HLA-A and HLA-C genes tended to predict GO in a gender-dependent manner in patients with GD in Taiwan.
These two patient groups were associated with similar HLA-A alleles and different HLA-DPB1 alleles, suggesting the presence of two genetic factors for GD within the HLA region; one is HLA-A linked and may be related to thyroid organ specificity, the other is HLA-DP linked and may control the severity of autoimmunity.
However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with Graves' disease has not been documented in any other ethnic group.
The aims of this study were to examine the HLA-A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis.
Using the technique of in vitro enzymatic DNA amplification and dot blot hybridization with sequence-specific oligonucleotide (SSO) probes, a study of genetic polymorphism of HLA-DPB1 was performed in 83 unrelated patients with Graves' disease (GD), 48 patients with early onset myasthenia gravis (EOMG) and 100 normal British caucasoid subjects who were also tissue typed for HLA-A, B and DR antigens.
To elucidate genetic differences among EO, Graves' disease (Gr) and Hashimoto's thyroiditis (H), we analysed HLA-A, B, C, DR, DQ, D and DP types in 23 Japanese EO patients, 88 Gr patients, 46 H patients and 186 control subjects utilizing assays of lymphocyte cytotoxicity and restriction fragment length polymorphism (RFLP).