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HLA-DRB1 Amino Acid Positions and Residues Associated with Antibody-positive Rheumatoid Arthritis in Black South Africans.

Authors
  • Govind, Nimmisha1, 2
  • Reynolds, Richard J3, 4
  • Hodkinson, Bridget3, 4
  • Ickinger, Claudia3, 4
  • Ramsay, Michele3, 4
  • Bridges, S Louis Jr3, 4
  • Tikly, Mohammed3, 4
  • 1 From the Division of Rheumatology, and Division of Human Genetics, Faculty of Health Sciences, and the Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA; University of Cape Town, Cape Town, South Africa. [email protected] , (South Africa)
  • 2 N. Govind, PhD, Division of Rheumatology, University of the Witwatersrand; R.J. Reynolds, PhD, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; B. Hodkinson, PhD, University of Cape Town; C. Ickinger, MBBCh, Division of Rheumatology, University of the Witwatersrand; M. Ramsay, PhD, Sydney Brenner Institute for Molecular Bioscience, and Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand;S.L. Bridges Jr., PhD, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; M. Tikly, PhD, Division of Rheumatology, University of the Witwatersrand. [email protected]
  • 3 From the Division of Rheumatology, and Division of Human Genetics, Faculty of Health Sciences, and the Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA; University of Cape Town, Cape Town, South Africa. , (South Africa)
  • 4 N. Govind, PhD, Division of Rheumatology, University of the Witwatersrand; R.J. Reynolds, PhD, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; B. Hodkinson, PhD, University of Cape Town; C. Ickinger, MBBCh, Division of Rheumatology, University of the Witwatersrand; M. Ramsay, PhD, Sydney Brenner Institute for Molecular Bioscience, and Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand;S.L. Bridges Jr., PhD, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; M. Tikly, PhD, Division of Rheumatology, University of the Witwatersrand.
Type
Published Article
Journal
The Journal of rheumatology
Publication Date
Feb 01, 2019
Volume
46
Issue
2
Pages
138–144
Identifiers
DOI: 10.3899/jrheum.180107
PMID: 30385709
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To investigate the association of specific amino acid positions, residues, and haplotypes of HLA-DRB1 in black South Africans with autoantibody-positive rheumatoid arthritis (RA). High-resolution HLA-DRB1 genotyping was performed in 266 black South Africans with autoantibody-positive RA and 362 ethnically and geographically matched controls. The alleles were converted to specific amino acid residues at polymorphic sites for downstream analyses. Logistic regression models were used to test whether variability at site, specific amino acid residues, and haplotypes (constructed from positions 11, 71, and 74) were associated with RA. Of the 29 amino acid positions examined, positions 11, 13, and 33 (permutation p = 3.4e-26, 1.2e-27, and 2.1e-28, respectively) showed the strongest association with RA. Univariate analyses of individual amino acid residues showed valine at position 11 (OR 5.1, 95% CI 3.7-7.0) and histidine at position 13 (OR 6.1, 95% CI 4.2-8.6) conferred the highest risk. The valine containing haplotypes of position 11, 71, 74, V_K_A conferred the most risk (OR 4.52, 95% CI 2.68-7.61) and conversely the haplotype with serine at this position, S_K_R, conferred the most protection (OR 0.83, 95% CI 0.61-1.15). Autoantibody-positive RA in black South Africans is associated with histidine at position 13 and valine at position 11 of HLA-DRB1, and haplotypes with valine at position 11 conferred the highest risk; conversely, serine at position 11 conveyed protection.

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