Elsevier

Human Immunology

Volume 39, Issue 3, March 1994, Pages 195-201
Human Immunology

Association of HLA-DPB1 ∗0501 with early-onset graves' disease in Japanese

https://doi.org/10.1016/0198-8859(94)90260-7Get rights and content

Abstract

To investigate the association between HLA antigens and Graves' disease among Japanese, serologic typing and DPB 1 genotyping using the PCR-RFLP method have been performed. HLA alleles of 106 patients with Graves' disease were determined, and the frequency of HLA-B46 was found to be significantly increased. Furthermore, the frequencies of HLA antigens were compared between two age groups: early-onset and late-onset patients (under and over 20 years, respectively). It was found that the frequency of DPB1∗0501 (88.9%) was significantly increased (pc < 0.004) in the early-onset group as compared with the healthy controls (55.0%) but not in the late-onset group (60.7%). On the other hand, a significant increase of HLA-B46 was observed in the late-onset patients (pc < 0.0004). These results suggest that the genetic background of Japanese patients with early-onset Graves' disease is different from late-onset patients. Namely, the HLA-DP allele (DPB 1∗0501) and the HLA-B allele (B46) are primarily involved in the pathogenesis of early-onset and late-onset Graves' disease in Japanese, respectively.

References (61)

  • H. Allannic et al.

    HLA and Graves' disease: an association with HLA-DRw3

    J Clin Endocrinol Metab

    (1980)
  • N.R. Farid et al.

    Graves' disease and HLA: clinical and epidemiologic associations

    Clin Endocrinol

    (1980)
  • B.R. Hawkins et al.

    Association of HLA antigens with thyrotoxic Graves' disease and periodic paralysis in Hong Kong Chinese

    Clin Endocrinol

    (1985)
  • P.P.B. Yeo et al.

    HLA Bw46 and DR9 associations in Graves' disease of Chinese patients are age- and sex-related

    Tissue Antigens

    (1989)
  • F.C. Grumet et al.

    HL-A antigens in Japanese patients with Graves' disease

    Tissue Antigens

    (1975)
  • A. Kawa et al.

    HLA-BW35 and B5 in Japanese patients with Graves' disease

    Acta Endocrinol

    (1977)
  • S. Naito et al.

    Japanese Graves' disease: association with HLA-Bw46

    Endocrinol Jpn

    (1987)
  • H. Shinagawa

    The effects of HLA class II genes on the susceptibility to the autoimmune thyroid diseases [in Japanese, with English abstract]

    Fukuoka Acta Med

    (1990)
  • H. Uno et al.

    Two major genes, linked to HLA and Gm, control susceptibility to Graves' disease

    Nature

    (1981)
  • P.I. Terasaki et al.

    Microdroplet assay of human serum cytotoxins

    Nature

    (1964)
  • P.I. Terasaki

    1970 microdroplet lymphocyte cytotoxicity test

  • P.I. Terasaki et al.

    Microdroplet testing for HLA-A, -B, -C, and -D antigens

    Am J Clin Pathol

    (1978)
  • F.H. Bach et al.

    Human T lymphocyte clones reactive in primed lymphocyte typing and cytotoxicity

    Nature

    (1979)
  • S. Shaw et al.

    Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogeneic proliferative and cytotoxic responses

    J Exp Med

    (1980)
  • R.K. Saiki et al.

    Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia

    Science

    (1985)
  • R.K. Saiki et al.

    Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase

    Science

    (1988)
  • U.B. Gyllensten et al.

    Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus

  • R.K. Saiki et al.

    Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes

  • N. Nomura et al.

    HLA-DQB1 genotyping by a modified PCR-RFLP method combined with group-specific primers

    Tissue Antigens

    (1991)
  • M. Ota et al.

    Modified PCR-RFLP method for HLA-DPB1 and -DQA1 genotyping

    Tissue Antigens

    (1991)

    • Cited by (51)

    • Neuromyelitis optica spectrum disorders

      2021, Journal of the Neurological Sciences
      Citation Excerpt :

      Aquaporin-4 IgG positivity is found to be associated with HLA-DRB1*03 (DR3) in French and Brazilian populations and HLA-DPB1*0501 in Japanese and Chinese populations [18]. These HLA haplotypes are also associated with other autoimmune disorders such as systemic lupus erythematosus (SLE) and Graves' disease [19]. Autoimmune conditions such as SLE, Myasthenia Gravis and Sjogren's syndrome are found in association with NMO [23] and these disorders are also more common in family members of patients with NMO [17].

    • Future Directions of Genomics Research in Rheumatic Diseases

      2017, Rheumatic Disease Clinics of North America
      Citation Excerpt :

      Although this region is only 0.1% of the length of the human genome, the MHC region confers most of the risk for most rheumatic diseases. The initial identification of the genetic risk loci was reported to be associated with the HLA genes located in the MHC region, such as HLA-DRB1 for RA,5 HLA-C for psoriasis,6 HLA-B for ankylosing spondylitis,7 and HLA-DPB1 for Graves disease.6 However, delineation of the detailed disease risk of HLA alleles has been challenging and controversial owing to the complex structures of the polymorphisms in the MHC region.

    • Ethnic differences in the clinical presentation of Graves' ophthalmopathy

      2012, Best Practice and Research: Clinical Endocrinology and Metabolism
      Citation Excerpt :

      A meta-analysis of these three alleles by Bednarczuk et al estimated that the combined OR for HLA-DRB1*03, DRB1*04 and DRB1*07 as risk factors for GO were 1.5 (95% confidence intervals 0.9–2.5), 0.9 (CI 0.6–1.6) and 0.8 (0.5–1.1) respectively, although none of them showed statistically significant association (P > 0.05).38 In Asian populations, the association of HLA with GD is less clear from the small studies done in Japanese, Korean and Chinese patients.39–45 The most prominent susceptibility allele in Caucasians, DRB1*03:01, has a much lower frequency in Asians, ranging from less than 3% in Japanese and Koreans to 4–9% in Chinese,46,47 and HLA-B*46 might be the only HLA allele associated with GD with good replications in Asians.44,48

    • Neoself Antigens Presented on MHC Class II Molecules in Autoimmune Diseases

      2024, Advances in Experimental Medicine and Biology

    • Significance of HLA in Graves’ disease and Graves’ orbitopathy in Asian and Caucasian populations – a systematic review

      2023, Frontiers in Immunology

    • Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules

      2022, Science Advances
    View all citing articles on Scopus
    View full text
    Copyright © 1994 Published by Elsevier Inc.