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Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis
Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394254/ https://www.ncbi.nlm.nih.gov/pubmed/37467720 http://dx.doi.org/10.1016/j.xcrm.2023.101114 |
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author | Akiyama, Yoshiyuki Sonehara, Kyuto Maeda, Daichi Katoh, Hiroto Naito, Tatsuhiko Yamamoto, Kenichi Morisaki, Takayuki Ishikawa, Shumpei Ushiku, Tetsuo Kume, Haruki Homma, Yukio Okada, Yukinori |
author_facet | Akiyama, Yoshiyuki Sonehara, Kyuto Maeda, Daichi Katoh, Hiroto Naito, Tatsuhiko Yamamoto, Kenichi Morisaki, Takayuki Ishikawa, Shumpei Ushiku, Tetsuo Kume, Haruki Homma, Yukio Okada, Yukinori |
author_sort | Akiyama, Yoshiyuki |
collection | PubMed |
description | Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10(−9)). The association is confirmed in a replication set of 26 cases and 1,026 controls (p = 0.014). Fine mapping demonstrates the contribution to the disease risk of a completely linked haplotype of three human leukocyte antigen HLA-DQβ1 amino acid positions, 71, 74, and 75 (OR = 1.94; p = 5 × 10(−8)) and of HLA-DPβ1 amino acid position 178, which tags HLA-DPB1∗04:02 (OR = 2.35; p = 7.5 × 10(−8)). The three HLA-DQβ1 amino acid positions are located together at the peptide binding groove, suggesting their functional importance in antigen presentation. Our study reveals genetic contributions to HIC risk that may be associated with class II MHC molecule antigen presentation. |
format | Online Article Text |
id | pubmed-10394254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103942542023-08-03 Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis Akiyama, Yoshiyuki Sonehara, Kyuto Maeda, Daichi Katoh, Hiroto Naito, Tatsuhiko Yamamoto, Kenichi Morisaki, Takayuki Ishikawa, Shumpei Ushiku, Tetsuo Kume, Haruki Homma, Yukio Okada, Yukinori Cell Rep Med Report Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10(−9)). The association is confirmed in a replication set of 26 cases and 1,026 controls (p = 0.014). Fine mapping demonstrates the contribution to the disease risk of a completely linked haplotype of three human leukocyte antigen HLA-DQβ1 amino acid positions, 71, 74, and 75 (OR = 1.94; p = 5 × 10(−8)) and of HLA-DPβ1 amino acid position 178, which tags HLA-DPB1∗04:02 (OR = 2.35; p = 7.5 × 10(−8)). The three HLA-DQβ1 amino acid positions are located together at the peptide binding groove, suggesting their functional importance in antigen presentation. Our study reveals genetic contributions to HIC risk that may be associated with class II MHC molecule antigen presentation. Elsevier 2023-07-18 /pmc/articles/PMC10394254/ /pubmed/37467720 http://dx.doi.org/10.1016/j.xcrm.2023.101114 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Report Akiyama, Yoshiyuki Sonehara, Kyuto Maeda, Daichi Katoh, Hiroto Naito, Tatsuhiko Yamamoto, Kenichi Morisaki, Takayuki Ishikawa, Shumpei Ushiku, Tetsuo Kume, Haruki Homma, Yukio Okada, Yukinori Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis |
title | Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis |
title_full | Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis |
title_fullStr | Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis |
title_full_unstemmed | Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis |
title_short | Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis |
title_sort | genome-wide association study identifies risk loci within the major histocompatibility complex region for hunner-type interstitial cystitis |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394254/ https://www.ncbi.nlm.nih.gov/pubmed/37467720 http://dx.doi.org/10.1016/j.xcrm.2023.101114 |
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