MHC Associations of Ankylosing Spondylitis in East Asians Are Driven By HLA-B Amino-Acid Position 97, Confirming Findings in European Descent Subjects
DC Field | Value | Language |
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dc.contributor.author | Wang, Geng | - |
dc.contributor.author | Cortes, Adrian | - |
dc.contributor.author | Bang, So-Young | - |
dc.contributor.author | Leo, Paul | - |
dc.contributor.author | Brown, Matthew | - |
dc.contributor.author | Kim, Tae-Hwan | - |
dc.contributor.author | Xu, Huji | - |
dc.date.accessioned | 2021-08-02T23:27:13Z | - |
dc.date.available | 2021-08-02T23:27:13Z | - |
dc.date.created | 2021-06-11 | - |
dc.date.issued | 2017-11-06 | - |
dc.identifier.issn | 2326-5191 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/30412 | - |
dc.description.abstract | 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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.title | MHC Associations of Ankylosing Spondylitis in East Asians Are Driven By HLA-B Amino-Acid Position 97, Confirming Findings in European Descent Subjects | - |
dc.type | Conference | - |
dc.contributor.affiliatedAuthor | Bang, So-Young | - |
dc.contributor.affiliatedAuthor | Kim, Tae-Hwan | - |
dc.identifier.wosid | 000411824103096 | - |
dc.identifier.bibliographicCitation | 2017 ACR/ARHP Annual Meeting | - |
dc.relation.isPartOf | 2017 ACR/ARHP Annual Meeting | - |
dc.relation.isPartOf | ARTHRITIS & RHEUMATOLOGY | - |
dc.citation.title | 2017 ACR/ARHP Annual Meeting | - |
dc.citation.conferencePlace | US | - |
dc.citation.conferenceDate | 2017-11-03 | - |
dc.type.rims | CONF | - |
dc.description.journalClass | 1 | - |
dc.identifier.url | 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/ | - |
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