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

PURPOSE: To evaluate the contributions of human leucocyte antigen (HLA) class I and II genes in the development of Graves’ ophthalmopathy (GO) in a Southern Chinese population. METHODS: Eight HLA loci were genotyped and analysed in 272 unrelated patients with Graves’ disease (GD) or the proptosis an...

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Detalles Bibliográficos
Autores principales: Huang, Xiaosheng, Liu, Guiqin, Mei, Shaoyi, Cai, Jiamin, Rao, Jing, Tang, Minzhong, Zhu, Tianhui, Chen, Wenchiew, Peng, Shiming, Wang, Yan, Ye, Ye, Zhang, Tong, Deng, Zhihui, Zhao, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Laboratory Science
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479741/
https://www.ncbi.nlm.nih.gov/pubmed/33221730
http://dx.doi.org/10.1136/bjophthalmol-2020-317091
Descripción
Sumario:PURPOSE: To evaluate the contributions of human leucocyte antigen (HLA) class I and II genes in the development of Graves’ ophthalmopathy (GO) in a Southern Chinese population. METHODS: 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. RESULTS: The allele frequencies of HLA-DRB1*16:02 and -DQB1*05:02 in the GD, proptosis and myogenic groups, HLA-B*38:02 and -DQA1*01:02 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 HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02 and HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01 in the proptosis and myogenic groups, and HLA-A*02:03-B*38:02-C*07:02 and 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 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 HLA-DRA1-DRB1*16:02 heterodimer, and the epitopes (‘ILEITDNPY’ of THSR, ‘NYALVIFEM’ and ‘NYSFYVLDN’ of IGF-1R) were also fitted exactly in the peptide-binding groove between HLA-DQA1*01:02-DQB1*05:02 heterodimer. CONCLUSIONS: The HLA-DRB1*16:02 and -DQB1*01:02 alleles might be risk factors for GD including the proptosis and myogenic phenotypes of GO. The alleles HLA-B*38:02, -DQA1*01:02, the HLA haplotypes consisting of HLA-B*38:02, -DRB1*16:02, -DQA1*01:02 and -DQB1*05:02 might be susceptibility risk factors for GO. Simultaneously, some epitopes of TSHR and IGF-1R tightly binding to groove of HLA-DRA1-DRB1*16:02 or HLA-DQA1*01:02-DQB1*05:02 heterodimers might provide some hints on presenting the pathological antigen in GO.

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