The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus

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 MethylEdge™ 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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The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus.

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 MethylEdge™ 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.

Association of NLRP3 single nucleotide polymorphisms with ulcerative colitis: A case-control study.

BACKGROUND: Ulcerative colitis (UC) is inflammatory bowel disease (IBD), characterized by chronic inflammation episodes within mucosal layer of the intestine mostly affecting colon and rectum. As the role of innate immunity in pathogenesis of disease and important role of NLRP3, the aim of this study is to investigate the association of NLRP3 SNPs with UC in Iranian patients. METHODS: Blood samples from 45 UC patients and 56 healthy subjects were tested for single nucleotide polymorphisms in rs10754558, rs3806265, rs4612666, and rs35829419 of NLRP3 gene, using real-time PCR method. RESULTS: Among the investigated SNPs, "GG" genotype of rs10754558 have been 2.48 times more common among UC patients (P=0.04), while "CG" genotype has indicated protective effect against UC, as more frequently found in healthy subjects. CONCLUSION: Despite no significant association between three investigated SNPs and disease, "GG" and "CG" genotypes of rs10754558 have been significantly associated with disease.