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Published in: Clinical Rheumatology 8/2019

01-08-2019 | Ankylosing Spondylitis | Original Article

Ankylosing spondylitis is associated with aberrant DNA methylation of IFN regulatory factor 8 gene promoter region

Authors: Mengya Chen, Meng Wu, Xingxing Hu, Jiajia Yang, Renfang Han, Yubo Ma, Xu Zhang, Yaping Yuan, Rui Liu, Guangming Jiang, Shengqian Xu, Jianhua Xu, Zongwen Shuai, Faming Pan

Published in: Clinical Rheumatology | Issue 8/2019

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Abstract

Objectives

To investigate the role of methylation levels of the IFN regulatory factor 8 (IRF8) gene promoter in the development of ankylosing spondylitis (AS).

Methods

In this study, we compared the methylation levels of the IRF8 gene promoter between 99 AS patients and 99 healthy controls using MethylTarget approach. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to compare the mRNA levels of the IRF8 gene in the other 19 AS patients and 19 healthy controls.

Results

Differential methylation was found in 91 CpG sites of the IRF8 gene promoter, and 4 CpG regions were highly methylated in AS patients compared to healthy controls (p < 0.05). In the verification stage, we found that the mRNA levels of the IRF8 gene in AS patients were significantly lower than that in controls (AS 0.77 (0.39–1.74), P = 0.038). Positive correlations between methylation of the IRF8 gene and the duration of disease, BASFI, and ESR were observed in AS patients.

Conclusions

We found a significant hypermethylation of the IRF8 gene promoter and a downregulation of the mRNA levels of the IRF8 gene in AS patients. This suggests that aberrant methylation of the IRF8 gene promoter may probably contribute to the development and pathogenesis of AS through regulating the expression of mRNA.
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Literature
15.
16.
go back to reference Hong KM, Kim HK, Park SY, Poojan S, Kim MK, Sung J, Tsao BP, Grossman JM, Rullo OJ, Woo JM, McCurdy DK, Rider LG, Miller FW, Song YW (2017) CD3Z hypermethylation is associated with severe clinical manifestations in systemic lupus erythematosus and reduces CD3zeta-chain expression in T cells. Rheumatology (Oxford, England) 56(3):467–476. https://doi.org/10.1093/rheumatology/kew405 CrossRef Hong KM, Kim HK, Park SY, Poojan S, Kim MK, Sung J, Tsao BP, Grossman JM, Rullo OJ, Woo JM, McCurdy DK, Rider LG, Miller FW, Song YW (2017) CD3Z hypermethylation is associated with severe clinical manifestations in systemic lupus erythematosus and reduces CD3zeta-chain expression in T cells. Rheumatology (Oxford, England) 56(3):467–476. https://​doi.​org/​10.​1093/​rheumatology/​kew405 CrossRef
17.
go back to reference Zhao M, Zhou Y, Zhu B, Wan M, Jiang T, Tan Q, Liu Y, Jiang J, Luo S, Tan Y, Wu H, Renauer P, Del Mar Ayala Gutierrez M, Castillo Palma MJ, Ortega Castro R, Fernandez-Roldan C, Raya E, Faria R, Carvalho C, Alarcon-Riquelme ME, Xiang Z, Chen J, Li F, Ling G, Zhao H, Liao X, Lin Y, Sawalha AH, Lu Q (2016) IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus. Ann Rheum Dis 75(11):1998–2006. https://doi.org/10.1136/annrheumdis-2015-208410 CrossRefPubMedPubMedCentral Zhao M, Zhou Y, Zhu B, Wan M, Jiang T, Tan Q, Liu Y, Jiang J, Luo S, Tan Y, Wu H, Renauer P, Del Mar Ayala Gutierrez M, Castillo Palma MJ, Ortega Castro R, Fernandez-Roldan C, Raya E, Faria R, Carvalho C, Alarcon-Riquelme ME, Xiang Z, Chen J, Li F, Ling G, Zhao H, Liao X, Lin Y, Sawalha AH, Lu Q (2016) IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus. Ann Rheum Dis 75(11):1998–2006. https://​doi.​org/​10.​1136/​annrheumdis-2015-208410 CrossRefPubMedPubMedCentral
18.
go back to reference Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, Reinius L, Acevedo N, Taub M, Ronninger M, Shchetynsky K, Scheynius A, Kere J, Alfredsson L, Klareskog L, Ekstrom TJ, Feinberg AP (2013) Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol 31(2):142–147. https://doi.org/10.1038/nbt.2487 CrossRefPubMedPubMedCentral Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, Reinius L, Acevedo N, Taub M, Ronninger M, Shchetynsky K, Scheynius A, Kere J, Alfredsson L, Klareskog L, Ekstrom TJ, Feinberg AP (2013) Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol 31(2):142–147. https://​doi.​org/​10.​1038/​nbt.​2487 CrossRefPubMedPubMedCentral
30.
go back to reference Steinman RM (2003) The control of immunity and tolerance by dendritic cell. Pathologie-biologie 51(2):59–60CrossRefPubMed Steinman RM (2003) The control of immunity and tolerance by dendritic cell. Pathologie-biologie 51(2):59–60CrossRefPubMed
42.
go back to reference Masumi A, Tamaoki S, Wang IM, Ozato K, Komuro K (2002) IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages. FEBS Lett 531(2):348–353CrossRefPubMed Masumi A, Tamaoki S, Wang IM, Ozato K, Komuro K (2002) IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages. FEBS Lett 531(2):348–353CrossRefPubMed
43.
go back to reference Bigley V, Maisuria S, Cytlak U, Jardine L, Care MA, Green K, Gunawan M, Milne P, Dickinson R, Wiscombe S, Parry D, Doffinger R, Laurence A, Fonseca C, Stoevesandt O, Gennery A, Cant A, Tooze R, Simpson AJ, Hambleton S, Savic S, Doody G, Collin M (2018) Biallelic interferon regulatory factor 8 mutation: a complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation. J Allergy Clin Immunol 141(6):2234–2248. https://doi.org/10.1016/j.jaci.2017.08.044 CrossRefPubMedPubMedCentral Bigley V, Maisuria S, Cytlak U, Jardine L, Care MA, Green K, Gunawan M, Milne P, Dickinson R, Wiscombe S, Parry D, Doffinger R, Laurence A, Fonseca C, Stoevesandt O, Gennery A, Cant A, Tooze R, Simpson AJ, Hambleton S, Savic S, Doody G, Collin M (2018) Biallelic interferon regulatory factor 8 mutation: a complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation. J Allergy Clin Immunol 141(6):2234–2248. https://​doi.​org/​10.​1016/​j.​jaci.​2017.​08.​044 CrossRefPubMedPubMedCentral
47.
go back to reference Mok A, Rhead B, Holingue C, Shao X, Quach HL, Quach D, Sinclair E, Graf J, Imboden J, Link T, Harrison R, Chernitskiy V, Barcellos LF, Criswell LA (2018) Hypomethylation of CYP2E1 and DUSP22 promoters associated with disease activity and erosive disease among rheumatoid arthritis patients. Arthritis Rheum 70(4):528–536. https://doi.org/10.1002/art.40408 CrossRef Mok A, Rhead B, Holingue C, Shao X, Quach HL, Quach D, Sinclair E, Graf J, Imboden J, Link T, Harrison R, Chernitskiy V, Barcellos LF, Criswell LA (2018) Hypomethylation of CYP2E1 and DUSP22 promoters associated with disease activity and erosive disease among rheumatoid arthritis patients. Arthritis Rheum 70(4):528–536. https://​doi.​org/​10.​1002/​art.​40408 CrossRef
Metadata
Title
Ankylosing spondylitis is associated with aberrant DNA methylation of IFN regulatory factor 8 gene promoter region
Authors
Mengya Chen
Meng Wu
Xingxing Hu
Jiajia Yang
Renfang Han
Yubo Ma
Xu Zhang
Yaping Yuan
Rui Liu
Guangming Jiang
Shengqian Xu
Jianhua Xu
Zongwen Shuai
Faming Pan
Publication date
01-08-2019
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 8/2019
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-019-04505-5

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