OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression
© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH..
Vogt-Koyanagi-Harada (VKH) disease is a severe autoimmune disease. Herein, whole-exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow-up next-generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10-30 , odds ratio = 3.12). Functional study showes that OR11H1-A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA-sequencing find that OR11H1-A63 markedly increased growth arrest and DNA-damage-inducible gamma (GADD45G) expression. Moreover, OR11H1-A63 activates the MAPK and NF-κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF-κB pathways. Collectively, this study suggests that the OR11H1-A63 missense mutation may increase susceptibility to VKH disease in a GADD45G-dependent manner.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 11 vom: 01. März, Seite e2306563 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Xingran [VerfasserIn] |
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| Links: |
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| Themen: |
GADD45G |
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| Anmerkungen: |
Date Completed 21.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202306563 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Vogt-Koyanagi-Harada (VKH) disease is a severe autoimmune disease. Herein, whole-exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow-up next-generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10-30 , odds ratio = 3.12). Functional study showes that OR11H1-A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA-sequencing find that OR11H1-A63 markedly increased growth arrest and DNA-damage-inducible gamma (GADD45G) expression. Moreover, OR11H1-A63 activates the MAPK and NF-κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF-κB pathways. Collectively, this study suggests that the OR11H1-A63 missense mutation may increase susceptibility to VKH disease in a GADD45G-dependent manner | ||
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| 700 | 1 | |a Liu, Xianyang |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a He, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Guannan |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qingfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Peizeng |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Shengping |e verfasserin |4 aut | |
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