Analysis of Epigenetic Changes in Vitamin D Pathway Genes in Rheumatoid Arthritis Patients.

BACKGROUND

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex etiopathogenesis launched by multiple risk factors, including epigenetic alterations. RA is possibly linked to vitamin D that is epigenetically active and may alter DNA methylation of certain genes. Therefore, the study aimed to evaluate the relationship between DNA methylation status of vitamin D signaling pathway genes (), vitamin D level and associations with RA.

MATERIALS AND METHODS

Totally 76 participants (35 RA patients and 41 healthy controls) were enrolled from a case-control vitamin D and gene polymorphisms study regarding age and vitamin D concentration. CpG islands in promoter regions of the genes were chosen for DNA methylation analysis by means of pyrosequencing. Chemiluminescent microplate immunoassay was used to assess 25(OH)D serum levels. RA clinical data, i.e. the disease activity score C-reactive protein 28 (DAS28 - CRP) as well as patient-reported outcome questionnaires were recorded.

RESULTS

The study showed similar methylation pattern in the promoter regions of vitamin D pathway genes in RA and control group with >0.05 ( gene 2.39% 2.48%, gene 16.02% 15.17% and 2.53% 2.41%). methylation intensity was significantly higher in compare to methylation intensity of and genes in both groups (<0.0001). A tendency of higher vitamin D concentration in cases having methylated 57.57±28.93 47.40±29.88 nmol/l), 53.23±26.22 48.23±34.41 nmol/l) and (60.41±30.73 44.54±27.63 nmol/l) genes and a positive correlation between methylation intensity and vitamin D level in RA affected participants was revealed (>0.05). A significantly higher methylation intensity (=0.0104) was detected in blood cells of vitamin D deficient (<50 nmol/l) RA patients vitamin D deficient controls.

CONCLUSIONS

Our data suggests some indirect associations between DNA methylation status of vitamin D pathway genes and vitamin D level in RA.