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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...

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Autores principales: Akiyama, Yoshiyuki, Sonehara, Kyuto, Maeda, Daichi, Katoh, Hiroto, Naito, Tatsuhiko, Yamamoto, Kenichi, Morisaki, Takayuki, Ishikawa, Shumpei, Ushiku, Tetsuo, Kume, Haruki, Homma, Yukio, Okada, Yukinori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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