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An intergenic variant rs9268877 between HLA-DRA and HLA-DRB contributes to the clinical course and long-term outcome of ulcerative colitis
DC Field | Value | Language |
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dc.contributor.author | Lee, Ho-Su | - |
dc.contributor.author | Yang, Suk-Kyun | - |
dc.contributor.author | Hong, Myunghee | - |
dc.contributor.author | Jung, Seulgi | - |
dc.contributor.author | Kim, Byoung Mok | - |
dc.contributor.author | Moon, Jung Won | - |
dc.contributor.author | Park, Sang Hyoung | - |
dc.contributor.author | Ye, Byong Duk | - |
dc.contributor.author | Oh, Seak Hee | - |
dc.contributor.author | Kim, Kyung Mo | - |
dc.contributor.author | Yoon, Yong Sik | - |
dc.contributor.author | Yu, Chang Sik | - |
dc.contributor.author | Baek, Jiwon | - |
dc.contributor.author | Lee, Cue Hyunkyu | - |
dc.contributor.author | Han, Buhm | - |
dc.contributor.author | Liu, Jianjun | - |
dc.contributor.author | Haritunians, Talin | - |
dc.contributor.author | McGovern, Dermot P. B. | - |
dc.contributor.author | Song, Kyuyoung | - |
dc.date.accessioned | 2023-04-25T07:32:19Z | - |
dc.date.available | 2023-04-25T07:32:19Z | - |
dc.date.created | 2019-09-04 | - |
dc.date.created | 2019-09-04 | - |
dc.date.created | 2019-09-04 | - |
dc.date.issued | 2018-09 | - |
dc.identifier.citation | Journal of Crohn's and Colitis, Vol.12 No.9, pp.1113-1121 | - |
dc.identifier.issn | 1873-9946 | - |
dc.identifier.uri | https://hdl.handle.net/10371/191516 | - |
dc.description.abstract | Background and Aims: The genetic contribution to the prognosis of ulcerative colitis [UC] is poorly understood, and most currently known susceptibility loci are not associated with prognosis. To identify genetic variants influencing the prognosis of UC, we performed an Immunochip-based study using an extreme phenotype approach. Methods: Based on the finding that the only association, Pdiscovery-meta < 1 x 10(-4), was located in the human leukocyte antigen [HLA], we focused our analyses on the HLA region. We performed the analysis using HLA imputation data from three independent discovery cohorts of 607 UC patients [243 poor-prognosis and 364 good-prognosis], followed by replication in 274 UC patients [145 poor-prognosis and 129 good-prognosis]. Results: We found that rs9268877, located between HLA-DRA and HLA-DRB, was associated with poor-prognosis of UC at genome-wide significance (odds ratio [ORdiscovery] = 1.82; ORreplication = 1.55; ORcombined-meta = 1.72, p(combined-meta) = 1.04 x 10-8), with effect size [OR] increasing incrementally according to worsening of prognosis in each of the three independent discovery cohorts and the replication cohort. However, rs9268877 showed no association with UC susceptibility [ORcombined-meta = 1.07, p(combined-meta) = 0.135]; rs9268877 influenced 30-year clinical outcomes, and the presence of the rs9268877 risk allele had a sensitivity of 80.0% and specificity of 38.1% for colectomy. Conclusions: Our results provide new insights into prognosis-associated genetic variation in UC, which appears to be distinct from the genetic contribution to disease susceptibility. These findings could be useful in identifying poor-prognosis patients who might benefit from early aggressive therapy. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier Science | - |
dc.title | An intergenic variant rs9268877 between HLA-DRA and HLA-DRB contributes to the clinical course and long-term outcome of ulcerative colitis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1093/ecco-jcc/jjy080 | - |
dc.citation.journaltitle | Journal of Crohn's and Colitis | - |
dc.identifier.wosid | 000443561000014 | - |
dc.identifier.scopusid | 2-s2.0-85055829422 | - |
dc.citation.endpage | 1121 | - |
dc.citation.number | 9 | - |
dc.citation.startpage | 1113 | - |
dc.citation.volume | 12 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Han, Buhm | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GENOME-WIDE ASSOCIATION | - |
dc.subject.keywordPlus | INFLAMMATORY-BOWEL-DISEASE | - |
dc.subject.keywordPlus | HOSPITAL-BASED COHORT | - |
dc.subject.keywordPlus | CROHNS-DISEASE | - |
dc.subject.keywordPlus | SUSCEPTIBILITY LOCI | - |
dc.subject.keywordPlus | GENETIC SUSCEPTIBILITY | - |
dc.subject.keywordPlus | TEMPORAL-CHANGE | - |
dc.subject.keywordPlus | PROGNOSIS | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | PREDICTORS | - |
dc.subject.keywordAuthor | Ulcerative colitis | - |
dc.subject.keywordAuthor | genetics | - |
dc.subject.keywordAuthor | biomarker | - |
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