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

• Published in: Genes and immunity Vol. 22; no. 2; pp. 101 - 107
• Main Authors: Xu, Shanshan, Gao, Xing, Ma, Yubo, Deng, Jixiang, Xu, Shengqian, Pan, Faming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2021; Nature Publishing Group
• Subjects: 631/208/176/1988; 631/208/199; Ankylosing spondylitis; Arthritis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; CpG Islands; Development and progression; DNA Methylation; Gene Expression; Genetic aspects; Health aspects; Histocompatibility antigen HLA; HLA-B27 Antigen; Human Genetics; Humans; Immunological research; Immunology; Methylation; Spondylitis, Ankylosing - genetics; TNF Receptor-Associated Factor 5 - genetics; Transcription; Tumor necrosis factor; Tumor necrosis factor receptors; China
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/s41435-021-00135-7

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 (
r
s
 = −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.