Dataset Information

OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

ABSTRACT: 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, P_combined = 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.

SUBMITTER: Li X

PROVIDER: S-EPMC10953539 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

Li Xingran X Wang Guoqing G Wang Xiaotang X Li Wanqian W Li Na N Liu Xianyang X Fan Wei W He Siyuan S Han Yue Y Su Guannan G Cao Qingfeng Q Yang Peizeng P Hou Shengping S

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240102 11

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, P<sub>combined</sub> = 7.83 × 10<sup>-30</sup> , odds ratio = 3.12). Functional ...[more]

PMID: 38168905

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Project description:PurposeAs an autoimmune disease, Vogt‒Koyanagi‒Harada disease (VKHD) is a main type of uveitis in many countries and regions, significantly impacting patient vision. At present, information regarding VKHD is still limited, and further research is needed. We conducted a bibliometric analysis to characterize the overall status, current trends, and current focus of VKHD research.MethodLiterature published from 1975 to 2022 was obtained from the Web of Science core collection and analysed with the R-language packages Bibliometrix, VOSviewer, and CiteSpace software.ResultsA total of 1050 papers on VKHD were retrieved from 261 journals, and 16,084 references were obtained from the papers in the original search. The average annual number of published articles was approximately 21.9, and the number of publications rapidly increased after 2004. The journal Ocular Immunology and Inflammation published the most papers on VKHD, while the American Journal of Ophthalmology has the highest citation frequency. The leading countries were Japan, China (PRC), and the United States of America (USA). Yang PZ from Chongqing Medical University was the most prolific and cited author. The most frequently cited study discussed revision of VKHD diagnostic criteria. An analysis of the highest frequency keywords showed that most research focused on the treatment, diagnosis, and pathogenesis of VKHD and its relationship with other related diseases. At present, the most urgent research direction is in the relationship between COVID-19 or COVID-19 vaccines and VKHD and the corresponding mechanisms underlying it.ConclusionUtilizing dynamic and visualization tools, bibliometrics provides a clear depiction of the research history, development trends, and research hotspots in VKHD It serves as a valuable tool for identifying research gaps and areas that necessitate further exploration. Our study revealed potential directions for future VKHD research, including investigating specific molecular mechanisms underlying the disease, exploring the clinical utility of optical coherence tomography angiography and other diagnostic techniques, and conducting clinical research on novel therapeutic drugs.

Dataset Information

OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

Publications

OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

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