HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease

PLoS One. 2019 May 15;14(5):e0216941. doi: 10.1371/journal.pone.0216941. eCollection 2019.

Abstract

The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves' disease [GD]: 71, Hashimoto's disease [HD]: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients (Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD (P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP β chain, might contribute to the molecular pathogenesis of early-onset AITD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Alleles*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Graves Disease / diagnosis
  • Graves Disease / genetics*
  • Graves Disease / immunology
  • Graves Disease / pathology
  • HLA-DP beta-Chains / classification
  • HLA-DP beta-Chains / genetics*
  • HLA-DP beta-Chains / immunology
  • Haplotypes
  • Hashimoto Disease / diagnosis
  • Hashimoto Disease / genetics*
  • Hashimoto Disease / immunology
  • Hashimoto Disease / pathology
  • Humans
  • Male
  • Polymorphism, Genetic*

Substances

  • HLA-DP beta-Chains
  • HLA-DPB1 antigen

Grants and funding

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (HI14C3417) to TGK, the St. Vincent's hospital, research institute of medical science foundation (SVHR-2018-12) to WKC, and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2018R1C1B5084422) to WKC. Statistical consultation was supported by the Department of Biostatistics of the Catholic Research Coordinating Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.