Circulating methylation levels of SPTBN1 are associated with inflammation in rheumatoid arthritis

SPTBN1 has been reported in a variety of diseases, but the association with rheumatoid arthritis (RA) is not yet available in the literature. Our work was to assess the correlation between cg19486047 of SPTBN1 methylation level and clinical characteristics of patients with RA. Methods: Peripheral blood samples were collected from 241 RA patients, 29 OA patients, and 30 HCs. Methylation levels were assessed by targeted methylation sequencing technique, and the Pearson and Spearman correlation were applied to evaluate the association with clinical indices. Results: In a whole blood methylation study of RA patients, cg19486047 showed increased methylation levels in RA patients compared with OAs and HCs. Seronegative RA patients, particularly those in remission, can be diagnosed using the methylation levels of SPTBN1 and the CpG sites within it. Targeted methylation sequencing also identified that all four CpGs located in the nearby region of cg19486047 are hypermethylated compared with HCs. Similarly, the proportion of the CCCC haplotype is significantly higher than OAs or HCs . The correlation between the methylation levels of the above CpGs and haplotypes and the age of onset were all statistically significant. Conclusion: The SPTBN1 gene is hypermethylated in RA patients, and the same phenomenon occurs at the associated CpG positions and haplotypes. The methylation levels of three of the CpGs were significantly correlated with CCP, which implies a new biomarker for precision medicine in RA is being discovered.