Allele-Specific Quantification of HLA-DRB1 Transcripts Reveals Imbalanced Allelic Expression That Modifies the Amino Acid Effects in HLA-DRβ1
DC Field | Value | Language |
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dc.contributor.author | Chun, Sehwan | - |
dc.contributor.author | Bang, So-Young | - |
dc.contributor.author | Ha, Eunji | - |
dc.contributor.author | Cui, Jing | - |
dc.contributor.author | Gu, Ki-Nam | - |
dc.contributor.author | Lee, Hye-Soon | - |
dc.contributor.author | Kim, Kwangwoo | - |
dc.contributor.author | Bae, Sang-Cheol | - |
dc.date.accessioned | 2021-08-02T08:26:16Z | - |
dc.date.available | 2021-08-02T08:26:16Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 2326-5191 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/7967 | - |
dc.description.abstract | Objective: HLA association fine-mapping studies have shown the effects of missense variants in HLA–DRB1 on rheumatoid arthritis (RA) susceptibility, prognosis, and autoantibody production. However, the phenotypic effects of expression changes in HLA–DRB1 remain poorly understood. Therefore, we investigated the allele-specific expression of HLA–DRB1 and its effect on an HLA–DRβ1 structure–associated trait in RA. Methods: We quantified the allele-specific expression of each HLA–DRB1 3-field classic allele in 48 Korean RA patients with anti–citrullinated protein antibodies (ACPAs) and 319 healthy European subjects by using both RNA sequencing and HLA–DRB1 genotype data to calculate the relative expression strength of multiple HLA–DRB1 alleles (n = 14 in Koreans and n = 25 in Europeans) in each population. The known association between ACPA level and alanine at position 74 of HLA–DRβ1 in ACPA-positive RA was revisited to understand the phenotypic effect of allele-specific expression of HLA–DRB1 by modeling multivariate logistic regression with the genomic dosage or relative expression dosage of Ala-74 in 2 independent sets of 1,723 Korean RA patients with ACPA. Results: The relative expression strength was highly allele-specific, causing imbalanced allelic expression in HLA–DRB1 heterozygotes. The association between HLA-DRβ1 Ala-74 and ACPA level in RA was better explained by relative expression dosage of Ala-74 than by the genomic dosage (change in Akaike's information criterion = −6.98). Moreover, the expression variance of Ala-74 in Ala-74 heterozygotes with no genomic variance of Ala-74 was significantly associated with ACPA level (P = 2.26 × 10(−3)). Conclusion: Our findings illustrate the advantage of integrating quantitative and qualitative changes in HLA–DRB1 into a single model for understanding HLA–DRB1 associations. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | John Wiley and Sons Ltd | - |
dc.title | Allele-Specific Quantification of HLA-DRB1 Transcripts Reveals Imbalanced Allelic Expression That Modifies the Amino Acid Effects in HLA-DRβ1 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Bae, Sang-Cheol | - |
dc.identifier.doi | 10.1002/art.41535 | - |
dc.identifier.scopusid | 2-s2.0-85100425581 | - |
dc.identifier.wosid | 000614115700001 | - |
dc.identifier.bibliographicCitation | Arthritis and Rheumatology, v.73, no.3, pp.381 - 391 | - |
dc.relation.isPartOf | Arthritis and Rheumatology | - |
dc.citation.title | Arthritis and Rheumatology | - |
dc.citation.volume | 73 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 381 | - |
dc.citation.endPage | 391 | - |
dc.type.rims | ART | - |
dc.type.docType | Article; Early Access | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Rheumatology | - |
dc.relation.journalWebOfScienceCategory | Rheumatology | - |
dc.subject.keywordPlus | amino acid | - |
dc.subject.keywordPlus | cyclic citrullinated peptide antibody | - |
dc.subject.keywordPlus | HLA DRB1 antigen | - |
dc.subject.keywordPlus | HLA DRB2 antigen | - |
dc.subject.keywordPlus | HLA DRB3 antigen | - |
dc.subject.keywordPlus | HLA DRB4 antigen | - |
dc.subject.keywordPlus | HLA DRB5 antigen | - |
dc.subject.keywordPlus | HLA DRB6 antigen | - |
dc.subject.keywordPlus | HLA DRB7 antigen | - |
dc.subject.keywordPlus | HLA DRB8 antigen | - |
dc.subject.keywordPlus | HLA DRB9 antigen | - |
dc.subject.keywordPlus | HLA DRbeta1 antigen | - |
dc.subject.keywordPlus | messenger RNA | - |
dc.subject.keywordPlus | tryptophan | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | alanine | - |
dc.subject.keywordPlus | cyclic citrullinated peptide antibody | - |
dc.subject.keywordPlus | HLA DRB1 antigen | - |
dc.subject.keywordPlus | messenger RNA | - |
dc.subject.keywordPlus | allele | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | disease association | - |
dc.subject.keywordPlus | expression quantitative trait locus | - |
dc.subject.keywordPlus | gene dosage | - |
dc.subject.keywordPlus | gene expression | - |
dc.subject.keywordPlus | gene frequency | - |
dc.subject.keywordPlus | genetic association | - |
dc.subject.keywordPlus | genetic transcription | - |
dc.subject.keywordPlus | genotype | - |
dc.subject.keywordPlus | heterozygote | - |
dc.subject.keywordPlus | high throughput sequencing | - |
dc.subject.keywordPlus | HLA system | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | limit of quantitation | - |
dc.subject.keywordPlus | major clinical study | - |
dc.subject.keywordPlus | phenotypic variation | - |
dc.subject.keywordPlus | population | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | protein function | - |
dc.subject.keywordPlus | rheumatoid arthritis | - |
dc.subject.keywordPlus | RNA sequencing | - |
dc.subject.keywordPlus | allele | - |
dc.subject.keywordPlus | Asian continental ancestry group | - |
dc.subject.keywordPlus | Caucasian | - |
dc.subject.keywordPlus | gene expression | - |
dc.subject.keywordPlus | genetics | - |
dc.subject.keywordPlus | immunology | - |
dc.subject.keywordPlus | metabolism | - |
dc.subject.keywordPlus | quantitative trait locus | - |
dc.subject.keywordPlus | rheumatoid arthritis | - |
dc.subject.keywordPlus | South Korea | - |
dc.subject.keywordPlus | statistical model | - |
dc.identifier.url | https://onlinelibrary.wiley.com/doi/10.1002/art.41535 | - |
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