Association of ZC3HAV1 single nucleotide polymorphisms with the susceptibility of Vogt-Koyanagi-Harada Disease

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Abstract

Background

Polymorphisms of genes related to the immune response have been reported to confer susceptibility to Vogt-Koyanagi-Harada (VKH) disease. This study was carried out to determine whether zinc finger CCCH-type containing antiviral 1 (ZC3HAV1) and tripartite motif-containing protein 25 (TRIM25) genetic polymorphisms are associated with this disease.

Methods

A total of 766 VKH patients and 909 healthy individuals were enrolled in this two-stage case-control study. Thirty-one tag single nucleotide polymorphisms (SNPs) of ZC3HAV1 and TRIM25 were genotyped by MassARRAY System and iPLEX Gold Genotyping Assay. Allele and genotype frequencies were analyzed by the χ ² test or Fisher’s exact test. Cochran-Mantel-Haenszel test was used to assess the pooled odds ratio (OR) in the combined study. A stratified analysis was performed in terms of the major clinical features of VKH disease.

Results

We found a statistically significant increased frequency of the minor A allele of ZC3HAV1 rs7779972 ( P = 1.50 × 10 ^− 4, pooled OR = 1.332, 95%CI = 1.149–1.545) in VKH disease as compared with controls by using the Cochran-Mantel-Haenszel test. The GG genotype of rs7779972 showed a protective association with VKH disease ( P = 1.88 × 10 ^− 3, OR = 0.733, 95%CI = 0.602–0.892). There was no difference regarding the frequency of the remaining SNPs between VKH cases and controls (all P > 2.08 × 10 ^− 3). The stratified analysis showed no significant association of rs7779972 with the major clinical characteristics of VKH disease.

Conclusion

Our study indicated that the ZC3HAV1 variant rs7779972 might confer susceptibility to VKH disease in Han Chinese.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12920-023-01546-3.

Related collections

Most cited references 33

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Interleukin-6: designing specific therapeutics for a complex cytokine

Christoph Garbers, Sylvia Heink, Thomas Korn … (2018)

Interleukin-6 (IL-6) is a pivotal cytokine with a diverse repertoire of physiological functions that include regulation of immune cell proliferation and differentiation. Dysregulation of IL-6 signalling is associated with inflammatory and lymphoproliferative disorders such as rheumatoid arthritis and Castleman disease, and several classes of therapeutics have been developed that target components of the IL-6 signalling pathway. So far, monoclonal antibodies against IL-6 or IL-6 receptor (IL-6R) and Janus kinases (JAK) inhibitors have been successfully developed for the treatment of autoimmune diseases such as rheumatoid arthritis. However, clinical trials of agents targeting IL-6 signalling have also raised questions about the diseases and patient populations for which such agents have an appropriate benefit-risk profile. Knowledge from clinical trials and advances in our understanding of the complexities of IL-6 signalling, including the potential to target an IL-6 trans-signalling pathway, are now indicating novel opportunities for therapeutic intervention. In this Review, we overview the roles of IL-6 in health and disease and analyse progress with several approaches of inhibiting IL-6-signalling, with the aim of illuminating when and how to apply IL-6 blockade.

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Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment.

Liping Du, Aize Kijlstra, Peizeng Yang (2016)

Vogt-Koyanagi-Harada (VKH) disease is one of the major vision-threatening diseases in certain populations, such as Asians, native Americans, Hispanics and Middle Easterners. It is characterized by bilateral uveitis that is frequently associated with neurological (meningeal), auditory, and integumentary manifestations. Although the etiology and pathogenesis of VKH disease need to be further elucidated, it is widely accepted that the clinical manifestations are caused by an autoimmune response directed against melanin associated antigens in the target organs, i.e. the eye, inner ear, meninges and skin. In the past decades, accumulating evidence has shown that genetic factors, including VKH disease specific risk factors (HLA-DR4) and general risk factors for immune mediated diseases (IL-23R), dysfunction of immune responses, including the innate and adaptive immune system and environmental triggering factors are all involved in the development of VKH disease. Clinically, the criteria of diagnosis for VKH disease have been further improved by the employment of novel imaging techniques for the eye. For the treatment, early and adequate corticosteroids are still the mainstream regime for the disease. However, immunosuppressive and biological agents have shown benefit for the treatment of VKH disease, especially for those patients not responding to corticosteroids. This review is focused on our current knowledge of VKH disease, especially for the diagnosis, pathogenesis (genetic factors and immune mechanisms), ancillary tests and treatment. A better understanding of the role of microbiome composition, genetic basis and ongoing immune processes along with the development of novel biomarkers and objective quantitative assays to monitor intraocular inflammation are needed to improve current management of VKH patients.

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Activation of the interleukin-23/interleukin-17 signalling pathway in autoinflammatory and autoimmune uveitis

Zhenyu Zhong, Guannan Su, Aize Kijlstra … (2021)

Uveitis is a group of diseases characterized by intraocular inflammation, of which some are driven by autoinflammatory or autoimmune responses, such as Vogt-Koyanagi-Harada disease, Behçet's disease, uveitis associated with spondyloarthritis, ocular sarcoidosis, sympathetic ophthalmia and birdshot chorioretinopathy. These entities have various clinical forms, but genetic and biomarker data suggest that they share a common molecular basis, activation of the Interleukin (IL)-23/IL-17 pathway. Multiple factors including genetic predisposition, various cytokine imbalances, infectious agents and gut alterations are found to trigger an aberrant response of this pathway. The enhanced activity of the IL-23/IL-17 pathway is committed to the expansion and pathogenicity of Th17 cells. Evidence from animal models demonstrates that the development of pathogenic Th17 cells is responsible for the induction of experimental autoimmune uveitis. Further findings indicate that retinal pigment epithelium (RPE) cells may be a target of IL-17. IL-17 triggers downstream inflammatory cascades and causes dysfunction of RPE cells, which may affect retinal barrier function and thereby promote intraocular inflammation. Currently, several emerging drugs blocking the IL-23/IL-17 pathway have been assessed for the treatment of uveitis in pilot studies. The purpose of this is to summarize updated biological knowledge and preliminary clinical data, providing the rationale for further development and evaluation of novel drugs targeting the IL-23/IL-17 pathway in autoinflammatory and autoimmune uveitis. Future studies may focus on translational medicine targeting the IL-23/IL-17 pathway for the improvement of diagnosis and treatment of uveitis. In conclusion, activation of the IL-23/IL-17 pathway is a critical biological event and can be an important target for the treatment of autoinflammatory and autoimmune uveitis.

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Author and article information

Contributors

Peizeng Yang: peizengycmu@126.com

Journal

Journal ID (nlm-ta): BMC Med Genomics

Journal ID (iso-abbrev): BMC Med Genomics

Title: BMC Medical Genomics

Publisher: BioMed Central (London )

ISSN (Electronic): 1755-8794

Publication date (Electronic): 23 May 2023

Publication date PMC-release: 23 May 2023

Publication date Collection: 2023

Volume: 16

Electronic Location Identifier: 113

Affiliations

[1 ]GRID grid.452206.7, ISNI 0000 0004 1758 417X, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, ; Chongqing, China

[2 ]GRID grid.256112.3, ISNI 0000 0004 1797 9307, Department of Ophthalmology & Optometry, The School of Medical Technology and Engineering, , Fujian Medical University, ; Fuzhou, P. R. China

Article

Publisher ID: 1546

DOI: 10.1186/s12920-023-01546-3

PMC ID: 10204004

PubMed ID: 37221558

SO-VID: cadd2c99-4708-4f53-9af5-5bd8bd4eab27

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 10 January 2023

Date accepted : 14 May 2023

Funding

Funded by: National Natural Science Foundation of China Major International (Regional) Joint Research Project

Award ID: 81720108009

Funded by: National Natural Science Foundation of China Key Program

Award ID: 81930023

Funded by: Chongqing Key Project

Award ID: CSTC2021jscx-gksb-N0010

Funded by: Chongqing Outstanding Scientists Project

Award ID: 2019

Funded by: Chongqing Chief Medical Scientist Project

Award ID: 2018

Funded by: Chongqing Science & Technology Platform and Base Construction Program

Award ID: cstc2014pt-sy10002

Funded by: Chongqing Key Laboratory of Ophthalmology

Award ID: CSTC, 2008CA5003

Custom metadata

ScienceOpen disciplines: Genetics

Keywords: zc3hav1,vogt-koyanagi-harada disease,single nucleotide polymorphisms,autoimmune,genetic susceptibility

Data availability: