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DNA methylation and transcription of the FOXO3a gene are associated with ankylosing spondylitis

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Abstract

To explore the association between methylation level and transcript level of Forkhead box O3a (FOXO3a) gene with ankylosing spondylitis (AS) susceptibility. Methylation levels of the FOXO3a promoter were measured in 84 AS patients and 83 healthy controls. A total of 77 patients and 66 healthy subjects were included in subsequent mRNA level testing. DNA methylation levels of 107 CpG sites on 6 CpG islands in the FOXO3a gene were investigated. This study indicated that CpG-4 and CpG-5 islands were markedly hypomethylated in AS patients. The methylation level of CpG-4 island in AS patients was negatively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Ankylosing Spondylitis Disease Activity Score (ASDAS). Moreover, FOXO3a mRNA levels were significantly decreased in AS patients and were obviously negatively correlated with the methylation levels of CpG-2 and CpG-5 islands in AS patients without treatment. The sensitivity and specificity of differential methylated CpG sites of FOXO3a were 74.7 and 85.4%, respectively. Besides, FOXO3a mRNA had a sensitivity of 80.0% and a specificity of 68.8%. DNA methylation and transcription of FOXO3a might be related to AS susceptibility and play a crucial role in the diagnosis of AS, but many open questions remain.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are deeply grateful to all the patients and healthy individuals who participated in our study. And we would like to acknowledgement the national natural science foundation of China for its financial support.

Funding

The study was sponsored by the National Natural Science Foundation of China (Grant No 82073655) and the Scientific Research Level upgrading Project of Anhui Medical University (Grant No 2020xkjT006).

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Author notes

  1. Shanshan Xu, Xiaoyi Zhang and Xinqi Wang contributed equally to this work and should be considered co-first author.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    Shanshan Xu, Xinqi Wang, Huimin Xie, Feier Wang, Tingting Zhou, Lingxiang Yu & Faming Pan

  2. The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    Shanshan Xu, Xinqi Wang, Huimin Xie, Feier Wang, Tingting Zhou, Lingxiang Yu & Faming Pan

  3. Department of Toxicology, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    Xiaoyi Zhang

  4. Department of Rheumatism and Immunity, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China

    Shengqian Xu

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  1. Shanshan Xu
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  2. Xiaoyi Zhang
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  9. Faming Pan
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Contributions

Study conception and design were performed by SX, XZ, XW, SX and FP. Material preparation and data collection were performed by SX, XZ, XW, XW, HX, FW, TZ and LY. Data analysis were performed by SX, XZ and XW. The first draft of the manuscript was written by SX and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Faming Pan.

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The authors declare no competing interests.

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All the subjects were given an informed consent and were well told of the study protocol.

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The study was approved by the Ethical Committee of Anhui Medical University (Hefei, China), and all procedures have complied with the 1964 Declaration of Helsinki.

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Xu, S., Zhang, X., Wang, X. et al. DNA methylation and transcription of the FOXO3a gene are associated with ankylosing spondylitis. Clin Exp Med 23, 483–493 (2023). https://doi.org/10.1007/s10238-022-00831-2

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  • DOI: https://doi.org/10.1007/s10238-022-00831-2

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