The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus
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Keywords
Systemic lupus erythematosus, FOXP3, Epigenetics, Methylation, Autoimmunity
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease caused by interaction of genetic, epigenetic, and environmental factors. One of the important epigenetic factors in SLE would be methylation of immune-related genes, such as FOXP3, which plays a role in activating the regulation and also the function of T cells. To date, the relationship between levels of serum bio-markers and the susceptibility to lupus in children has not been well-understood. In this study, the involvement of etiologic factors, such as methylation of FOXP3 gene, was investigated in children with SLE.
Method: Twenty-four female children with SLE and 25 female healthy subjects without any history of autoimmune and inflammatory diseases were included in this study. Blood samples were obtained and DNA was extracted from the blood cells. The bisulphite method was used to convert the DNA using the MethylEdgeTM Bisulfite Conversion System Kit. Then, methylation of the gene was investigated using Real-Time methylation-specific PCR.
Results: The FOXP3 DNA methylation in patients and healthy subjects was significantly different. While the median unmethylated DNA in patients was 0.57 ± 0.43, it was 0.97 ± 0.83 in healthy subjects (P = 0.012). The Demethylation Index in patients was 0.007 ± 0.003, significantly lower than in controls (0.014 ± 0.013; P = 0.012).
Conclusions: The FOXP3 gene methylation in children with SLE was significantly higher than healthy subjects, which could possibly affect the level of gene expression. Therefore, one of the causes of increased immune response in SLE can be the lower expression of FOXP3 by hypermethylation of this gene.
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