Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis

Background Genetic and epigenetic factors are strongly associated with the autoimmune disease rheumatoid arthritis (RA). Cyclic AMP response element modulator (CREM), a gene related to immune system regulation, has been implicated in various immune‐mediated inflammatory processes, although it remains unknown whether CREM is involved in RA. Methods This study enrolled 278 RA patients and 262 controls. Three variants [rs12765063, rs17499247, rs1213386] were identified through linkage disequilibrium and expression quantitative trait locus analysis, and CREM transcript abundance was determined by quantitative real‐time polymerase chain reaction. The identified variants were genotyped using the TaqMan Allelic Discrimination assay, and CREM promoter methylation was assessed by bisulphite sequencing. Differences between groups and correlations between variables were assessed with Student's t‐tests and Pearson's correlation coefficients. Associations between phenotypes and genotypes were evaluated with logistic regression. Results Rheumatoid arthritis patients exhibited increased CREM expression (p