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Association of methylation level and transcript level in TRAF5 gene with ankylosing spondylitis: a case-control study

Abstract

To explore the association between methylation level and transcript level of TNF receptor-associated factor 5 (TRAF5) gene with ankylosing spondylitis (AS) in Chinese Han population. Methylation and mRNA expression level of the TRAF5 gene were tested in 98 patients and 98 healthy controls. Among the 21 CpG sites, methylation levels at eight sites were significantly different between AS patients and healthy controls. However, only three sites remained significantly different after the correction by the Benjamini–Hochberg method. Compared with controls, the CpG island of TRAF5 gene promoter was highly methylated in AS patients, and the relative mRNA expression level of TRAF5 was significantly reduced in AS patients. And the mRNA level was negatively correlated with the methylation level of TRAF5 gene in AS patients (rs = −0.453, P < 0.001). Subgroup analyses indicated that there was no significant difference in the level of methylation between groups of different status of HLA-B27 and medications in AS patients. Multiple linear regression showed that disease-modifying antirheumatic drugs could reduce methylation levels of AS patients after adjusting for the effects of other drugs. In conclusion, the hypermethylation of the TRAF5 might contribute to the pathogenesis of AS, but many open questions remain.

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Fig. 1: Methylation levels of eight CpG sites on the TRAF5 island.
Fig. 2: The methylation levels of TRAF5 promoter region in AS and healthy controls.
Fig. 3: Results of TRAF5 mRNA expression levels, correlation analysis, and ROC analysis.

Data availability

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 controls who participated in our study. And we would like to acknowledge the National Natural Science Foundation of China for its financial support.

Funding

The study was sponsored by the National Natural Science Foundation of China (82073655 and 81773514) and the Scientific Research Level upgrading Project of Anhui Medical University (2020xkjT006).

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Correspondence to Faming Pan.

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

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Xu, S., Gao, X., Ma, Y. et al. Association of methylation level and transcript level in TRAF5 gene with ankylosing spondylitis: a case-control study. Genes Immun 22, 101–107 (2021). https://doi.org/10.1038/s41435-021-00135-7

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