ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 2918

Fine-Mapping Major Histocompatibility Complex Associations in ACPA-Positive Rheumatoid Arthritis Identified Shared HLA Amino Acid Polymorphisms in Asian and European Populations

Yukinori Okada1, Kwangwoo Kim2, Buhm Han3, Nisha E. Pillai4, Rick T-H. Ong4, Woei-Yuh Saw4, Ma Luo5, Lei Jiang6, Jian Yin6, So-Young Bang7, Hye-Soon Lee7, Matthew A. Brown8, Sang-Cheol Bae2, Huji Xu9, Yik-Ying Teo4, Paul IW. de Bakker10 and Soumya Raychaudhuri3, 1Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, 2Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 3Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 4National University of Singapore, Singapore, Singapore, 5University of Manitoba, Winnipeg, MB, Canada, 6The Second Military Medical University, Shanghai, China, 7Department of Rheumatology, Hanyang University Guri Hospital, Guri, South Korea, 8University of Queensland Diamantina Institute, Brisbane, Australia, 9Shanghai Changzheng Hospital, Shanghai, China, 10Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ACPA, genetics, human leukocyte antigens (HLA), major histocompatibility complex (MHC) and rheumatoid arthritis (RA)

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis II: Citrullination, Autoantibodies and Genes

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) risk is strongly associated with variations within the major histocompatibility complex (MHC) region, and in particular to HLA-DRB1 alleles. We aimed to fine-map RA risk alleles within the MHC in Asian populations and conduct trans-ethnic risk comparison to those in European populations.

Methods: We analyzed 2,782 anti-citrullinated protein antibodies (ACPA)-positive RA cases and 4,315 controls from Chinese and Korean populations. We applied HLA imputation to infer genotypes at eight class I and II HLA genes (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1) using SNP2HLA software and a newly constructed pan-Asian imputation reference panel.

Results: We obtained highly accurate imputation of HLA classical alleles with this reference panel (95.1% and 82.4% concordance for two and four digit classical alleles respectively). We observed the most significant association in HLA-DRb1 at amino acid position 13 (Pomnibus = 6.9×10-135), located outside the classical shared epitope (SE). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His>Phe>Arg>Tyr≈Gly>Ser) – but Asian effects are generally smaller. Applying stepwise conditional analysis, we identified additional associations at positions 57 (conditional Pomnibus = 2.2×10-33) and 74 (conditional Pomnibus = 1.1×10-8). Outside of HLA-DRb1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8×10-6) and HLA-DPb1 (Phe9, conditional P = 3.0×10-5) concordant with European populations. While a common set of amino-acid residue effects in three HLA genes are shared between European and Asian populations, these same effects can induce different classical allelic associations (e.g. HLA-DRB1*09:01) in the two populations due to differences in allele frequencies.

Conclusion: Our trans-ethnic study reveals that a common set of amino-acid residue effects in three HLA genes are largely shared between European and Asian populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC.


Disclosure:

Y. Okada,
None;

K. Kim,
None;

B. Han,
None;

N. E. Pillai,
None;

R. T. H. Ong,
None;

W. Y. Saw,
None;

M. Luo,
None;

L. Jiang,
None;

J. Yin,
None;

S. Y. Bang,
None;

H. S. Lee,
None;

M. A. Brown,
None;

S. C. Bae,
None;

H. Xu,
None;

Y. Y. Teo,
None;

P. I. de Bakker,
None;

S. Raychaudhuri,
None.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/fine-mapping-major-histocompatibility-complex-associations-in-acpa-positive-rheumatoid-arthritis-identified-shared-hla-amino-acid-polymorphisms-in-asian-and-european-populations/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology