Hypermethylation of the miR-155 gene in the whole blood and decreased plasma level of miR-155 in rheumatoid arthritis.

Abstract

OBJECTIVES:miR-155 plays a critical role in the inflammatory process and in diseases such as rheumatoid arthritis (RA). miR155 gene expression is regulated by its gene promoter region CpG island methylation. Previous studies have shown inconsistent changes in circulating levels of mir-155 in RA patients. The aims of our study were to evaluate miR-155 levels in plasma, to investigate its gene methylation level, and to correlate these levels with RA disease activity. METHODS:One hundred and twenty-five patients with RA, and 30 age and sex-matched healthy controls (HC) were enrolled. Whole blood and plasma samples were collected and stored at -80°C until analysis. DAS28 score at the time of the blood draw was used to assess RA disease activity. The methylation status of miR-155 host gene was determined in whole blood by quantitative real-time methylation-specific PCR (qPCR). miR-155 expression levels were evaluated by quantitative reverse transcription PCR. RESULTS:We found significantly lower circulating miR155 levels in RA patients compared to HC. Interestingly, the miR-155 gene methylation level was significantly higher in RA patients than in HC. miR-155 levels did not correlate with ACPA or RF positivity or disease activity. CONCLUSIONS:We show here higher miR-155 methylation in whole blood and lower plasma miR155 expression in RA patients in comparison to HC. The evaluation of miR-155 host gene methylation status or miR155 plasma level might be a potentially useful marker in RA determination.