ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1572

MHC Associations of Ankylosing Spondylitis in East Asians Are Driven By HLA-B Amino-Acid Position 97, Confirming Findings in European Descent Subjects

Geng Wang1, Adrian Cortes2, So-Young Bang3, Paul Leo4, Matthew Brown4, Tae-Hwan Kim5 and Huji Xu1, 1Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China, 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 3Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South), 4Translational Genomics Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, Australia, 5Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South)

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Monday, November 6, 2017

Title: Spondyloarthropathies and Psoriatic Arthritis – Pathogenesis, Etiology Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Whilst HLA-B27 is the MHC allele associated with AS, there is strong evidence indicating that other HLA-B alleles and MHC genes are involved in the disease. Large studies in European case-control cohorts have demonstrated risk associations with HLA-B*40 and multiple other HLA-B, -A and class II alleles, and demonstrated that in that ethnic group the amino-acid sequence at position 97 in HLA-B is the key determinant of HLA associations with AS (Cortes et al, Nat Com, 2015). A recent study in Korean AS cases and controls additionally identified association at HLA-C*15:02 (Kim et al, Arthritis Res Ther, 2015). In the current study, we examined in an expanded East Asian cohort the MHC associations of AS.

Methods: 1637 Chinese, Taiwanese and Korean AS cases meeting the modified New York Criteria for AS, and 1589 ethnically matched controls, were genotyped with the Illumina Immunochip, including a dense coverage of the MHC region. HLA genotypes and amino-acid composition was imputed using the SNP2HLA program using the Korean HLA reference panel (n=413) and association tested using logistic regression using 10 principal components to control for population stratification effects. Only HLA types with imputation information scores >0.8 were considered.

Results: Strong association was seen with HLA-B*27 (odds ratio (OR) 158, P=10-127). Controlling for this association, risk association is seen with HLA-B*40 (OR=8.22, P=7.66×10-83). Controlling for both HLA-B*27 and –B*40, no other HLA-B associations are seen (P>0.05). At amino-acid level the strongest association seen in uncontrolled analysis was with histidine or tyrosine at position 9 in HLA-B (p=10-155), but association at P<10-100 was seen with multiple HLA-B amino acids at P<10-100 including asparagine (found on HLA-B*27 alleles) at position 97, previously reported to be the main amino-acid determining HLA-B associations with AS. Controlling for HLA-B27 alone, or with –B27 and –B40, the strongest HLA amino-acid association remains with HLA-B position 97 (serine, found on HLA-B*7, *8, *15, *2707, *40, *41, *48; P=10-115 and 10-71 respectively)

Conclusion: This study confirms in East Asians that the primary amino-acid driver of HLA associations in AS is amino-acid position 97, which remains associated with AS independently of both HLA-B*27 and –B*40, the two key driver alleles in this ethnicity.

Disclosure: G. Wang, None; A. Cortes, None; S. Y. Bang, None; P. Leo, None; M. Brown, None; T. H. Kim, None; H. Xu, None.

To cite this abstract in AMA style:

Wang G, Cortes A, Bang SY, Leo P, Brown M, Kim TH, Xu H. MHC Associations of Ankylosing Spondylitis in East Asians Are Driven By HLA-B Amino-Acid Position 97, Confirming Findings in European Descent Subjects [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/mhc-associations-of-ankylosing-spondylitis-in-east-asians-are-driven-by-hla-b-amino-acid-position-97-confirming-findings-in-european-descent-subjects/. Accessed .

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