Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves' disease and Hashimoto's thyroiditis in the Japanese population.

ABSTRACT

The effects of amino acid variants encoded by human leukocyte antigen (HLA) class II on the development of Graves' disease (GD) and Hashimoto's thyroiditis (HT) have not been fully elucidated. We investigated the HLA-DRB1 genes of 243 GD patients and 82 HT patients in the Japanese population and compared the frequencies of HLA-DRB1 alleles and HLA-DRB1 amino acid variants between these patients and the Japanese populations previously reported by another institution. The frequencies of HLA-DRB1*0405 and -DRB1*1403 alleles were significantly higher and those of HLA-DRB1*0101 and -DRB1*1502 alleles were lower in GD patients than in controls. The frequencies of HLA-DRB1*0803 and -DRB1*0901 alleles were significantly higher and that of the HLA-DRB1*1302 allele was lower in HT patients than in controls. A blind association analysis with all amino acid positions identified DRß9 and DRß31 for GD and DRß9, DRß13, and DRß21 for HT. The frequency of Glu-9 was significantly higher and that of Cys-9 was lower in GD patients than in controls. The frequencies of Lys-9 and Phe-13 were significantly higher in HT patients than in controls. DRß9 and DRß13 could be critical amino acid positions in the development of GD and HT.