Arginine at position 74 of the HLA-DR β1 chain is associated with Graves' disease

Y. Ban, T. F. Davies, D. A. Greenberg, E. S. Concepcion, R. Osman, T. Oashi, Yaron Tomer

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Graves' disease (GD) is associated with HLA-DR3 (DRB1*03) in Caucasians, but the exact amino-acid sequence in the DR β 1 chain conferring susceptibility to GD is unknown. Therefore, the aim of our study was to identify the critical sequence among the HLA-DRB1 amino-acid residues occupying the peptide-binding pocket, which conferred susceptibility to GD. We sequenced the HLA-DRB1 locus in 208 Caucasian GD patients and 149 Caucasian controls. Sequence analysis showed an increased frequency of DR β-Arg-74 in GD patients compared to controls (41.8 and 13.4%, respectively; P = 2.3 × 10-8, OR = 4.6). Moreover, subset analyses showed that DR β-Arg-74 was also significantly more frequent in the HLA-DR3 negative GD patients than in controls (7.6 vs 0.8%, P = 0.02, OR = 10.5), suggesting that the association with DR β-Arg-74 is independent of the association with HLA-DR3. Structural modeling studies demonstrated that the change at position 74 from the neutral amino acids Ala or Gln to the positively charged amino-acid Arg significantly modifies the three-dimensional structure of the DR peptide-binding pocket. Our results suggested that structural heterogeneity of-the DR β-chain peptide-binding pocket P4 at residue 74 predispose some at risk individuals to GD.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalGenes and Immunity
Volume5
Issue number3
DOIs
StatePublished - May 2004
Externally publishedYes

Fingerprint

Graves Disease
HLA-DR Antigens
Arginine
HLA-DR3 Antigen
HLA-DRB1 Chains
Peptides
Neutral Amino Acids
Amino Acids
Sequence Analysis
Amino Acid Sequence

Keywords

  • Association
  • Autoimmunity
  • Gene
  • Graves' disease
  • HLA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Ban, Y., Davies, T. F., Greenberg, D. A., Concepcion, E. S., Osman, R., Oashi, T., & Tomer, Y. (2004). Arginine at position 74 of the HLA-DR β1 chain is associated with Graves' disease. Genes and Immunity, 5(3), 203-208. https://doi.org/10.1038/sj.gene.6364059

Arginine at position 74 of the HLA-DR β1 chain is associated with Graves' disease. / Ban, Y.; Davies, T. F.; Greenberg, D. A.; Concepcion, E. S.; Osman, R.; Oashi, T.; Tomer, Yaron.

In: Genes and Immunity, Vol. 5, No. 3, 05.2004, p. 203-208.

Research output: Contribution to journalArticle

Ban, Y, Davies, TF, Greenberg, DA, Concepcion, ES, Osman, R, Oashi, T & Tomer, Y 2004, 'Arginine at position 74 of the HLA-DR β1 chain is associated with Graves' disease', Genes and Immunity, vol. 5, no. 3, pp. 203-208. https://doi.org/10.1038/sj.gene.6364059
Ban Y, Davies TF, Greenberg DA, Concepcion ES, Osman R, Oashi T et al. Arginine at position 74 of the HLA-DR β1 chain is associated with Graves' disease. Genes and Immunity. 2004 May;5(3):203-208. https://doi.org/10.1038/sj.gene.6364059
Ban, Y. ; Davies, T. F. ; Greenberg, D. A. ; Concepcion, E. S. ; Osman, R. ; Oashi, T. ; Tomer, Yaron. / Arginine at position 74 of the HLA-DR β1 chain is associated with Graves' disease. In: Genes and Immunity. 2004 ; Vol. 5, No. 3. pp. 203-208.
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