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Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus

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Abstract

Background

As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood.

Objective

We aimed to investigate the possible significance of SLE’s DNA methylation and gain further insight into potential SLE-related biomarkers and therapeutic targets.

Methods

We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people.

Results

702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE.

Conclusions

Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the members for their generous participation.

Funding

This work was supported by the Zhejiang Key Research Project of Traditional Chinese Medicine and Zhejiang Traditional Chinese Medical Modernization Special Project Funding. (Grant numbers [2021ZZ015] and [2020ZX008]).

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Author notes

  1. Ting Fang and Suyi Liu have contributed equally to this work.

Authors and Affiliations

  1. The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China

    Ting Fang, Suyi Liu, Liying Chen, Yating Ren, Dingqi Lu, Xinyi Yao, Tao Hong & Xvfeng Zhang

  2. Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China

    Zhimin Xie, Kepeng Yang & Xinchang Wang

Authors
  1. Ting Fang
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  2. Suyi Liu
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Contributions

All authors provided contributions to this research and approved the final manuscript.

Corresponding author

Correspondence to Xinchang Wang.

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Conflict of interest

There are no relevant interests for the authors to disclose.

Ethical approval

The ethics committee of The Second Affiliated Hospital of Zhejiang Chinese Medical University has approved this study (No.2020-KL-076–01). All individual participants enrolled in the study obtained informed consent.

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Fang, T., Liu, S., Chen, L. et al. Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus. Genes Genom 45, 1187–1196 (2023). https://doi.org/10.1007/s13258-023-01407-4

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  • DOI: https://doi.org/10.1007/s13258-023-01407-4

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