Human leucocyte antigen alleles confer susceptibility and progression to Graves' ophthalmopathy in a Southern Chinese population.

Abstract

To evaluate the contributions of human leucocyte antigen (<i>HLA</i>) class I and II genes in the development of Graves' ophthalmopathy (GO) in a Southern Chinese population. Eight HLA loci were genotyped and analysed in 272 unrelated patients with Graves' disease (GD) or the proptosis and myogenic phenotypes of GO, and 411 ethnically matched control subjects. The allele frequencies of <i>HLA-DRB1*16:02</i> and <i>-DQB1*05:02</i> in the GD, proptosis and myogenic groups, <i>HLA-B*38:02</i> and <i>-DQA1*01:02</i> in the myogenic group were significantly higher than those in the control group, respectively (all corrected p values <0.05, OR >2.5). The haplotype frequencies of <i>HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02</i> and <i>HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01</i> in the proptosis and myogenic groups, and <i>HLA-A*02:03-B*38:02-C*07:02</i> and <i>HLA-A*02:03-B*38:02-C*07:02-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01</i> in the myogenic group were significantly higher than those in the control group respectively (all corrected p values <0.05, OR >2.5). The potential epitopes ('FLGIFNTGL' of TSHR, 'IRHSHALVS', 'ILYIRTNAS' and 'FVFARTMPA' of IGF-1R) were fitted exactly in the peptide-binding groove between <i>HLA-DRA1-DRB1*16:02</i> heterodimer, and the epitopes ('ILEITDNPY' of THSR, 'NYALVIFEM' and 'NYSFYVLDN' of IGF-1R) were also fitted exactly in the peptide-binding groove between <i>HLA-DQA1*01:02-DQB1*05:02</i> heterodimer. The <i>HLA-DRB1*16:02</i> and <i>-DQB1*01:02</i> alleles might be risk factors for GD including the proptosis and myogenic phenotypes of GO. The alleles <i>HLA-B*38:02, -DQA1*01:02</i>, the HLA haplotypes consisting of <i>HLA-B*38:02, -DRB1*16:02, -DQA1*01:02</i> and <i>-DQB1*05:02</i> might be susceptibility risk factors for GO. Simultaneously, some epitopes of TSHR and IGF-1R tightly binding to groove of <i>HLA-DRA1-DRB1*16:02</i> or <i>HLA-DQA1*01:02-DQB1*05:02</i> heterodimers might provide some hints on presenting the pathological antigen in GO.