Significant hypomethylation of gene promoter in patients with systemic lupus erythematosus.

OBJECTIVE

Scholars are exploring novel diagnostic and prognostic biomarkers with higher sensitivity and specificity for systemic lupus erythematosus (SLE). In this regard, DNA methylation alterations have aroused attention. The association between the dysfunction of and genes and SLE has been previously demonstrated. Therefore, in this study, we investigated the methylation level of and promoters in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls.

METHODS

Eighty Iranian SLE patients and 77 healthy individuals were enrolled. The methylation quantification endonuclease-resistant DNA (MethyQESD) method was used to assess methylation levels of and in extracted DNA of PBMCs. To quantify the diagnostic utility of the promoter methylation level of these genes, the receiver operating characteristic (ROC) curve was constructed.

RESULTS

promoter was significantly hypomethylated in SLE patients compared with healthy people ( < 0.001), while there was no significant difference in terms of promoter methylation levels ( = 0.167). Also, this differential methylation was observed in patients with renal involvement and patients without renal involvement (42.07 ± 25.73 vs 56.74 ± 29.71, = 0.007). ROC analyses indicated that the diagnostic power of the promoter methylation level for SLE was 0.839 [95% CI (0.781-0.911)]. Moreover, methylation level was negatively correlated with creatinine and anti-dsDNA concentration and positively correlated with C3 and C4 levels.

CONCLUSION

The results of this study highlight the application of methylation level in PBMCs of SLE patients as a diagnostic biomarker.