The Association between the Plasma Sugar and Lipid Profile with the Gene Expression of the Regulatory Protein of mTOR (Raptor) in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoinflammatory and self-perpetuating disease with both articular and extra-articular manifestations, such as cardiovascular complications, which are the leading cause of mortality and morbidity in RA patients. Impaired sugar and lipid metabolism are considered as the critical risk factors for cardiovascular disease (CVD). Regarding the regulatory function of Raptor in the immunometabolism, in this study, we evaluated the association between plasma sugar and lipid profiles with the gene expression of Raptor and the cytokine tumor necrosis factor-α (TNF-α), as an inflammatory mediator, in peripheral blood leukocyte of RA patients. MATERIAL AND METHODS: Thirty-five RA patients who received combinational disease modified anti-rheumatoid drugs (DMARD) regimen and thirty healthy subjects enrolled in this study. The gene expression of Raptor was assessed by the real-time PCR method, and the Plasma levels of glucose and lipids, as well as TNF-α, were obtained using Hitachi device and enzyme-linked immunosorbent assay (ELISA) technique, respectively. RESULTS: The gene expression of Raptor was reduced significantly in RA patients compared to the healthy subjects (p = .001). The plasma level of HDL was significantly higher in RA patients than the control group (p = .001), while the plasma level of LDL was reduced significantly in these patients (p = .001). CONCLUSION: In our study, the reduced gene expression of Raptor may contribute to the impaired immunometabolism in RA patients, which is independent of plasma sugar and lipid profile.

DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA.

DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.