title: Types of DNA methylation status of the interspersed repetitive sequences for LINE-1, Alu, HERV-E and HERV-K in the neutrophils from systemic lupus erythematosus patients and healthy controls.
abstract: Changes of the DNA methylation at the interspersed repetitive sequences can occur in various conditions including cancer as well as autoimmune diseases. We previously reported the hypomethylation of LINE-1 and HERV-E in the lymphocytes of systemic lupus erythematosus (SLE) patients. As neutrophils are another important cell type contributing to SLE pathogenesis, in this study, we evaluated the methylation levels and patterns for LINE-1, ALU, HERV-E and HERV-K in the neutrophils from SLE patients compared with the healthy controls. We observed that the methylation levels, especially for LINE-1, in the neutrophils from SLE patients were significantly lower than the healthy controls (P-value < 0.0001). Interestingly, this hypomethylation was not correlated with the activity of the disease. Furthermore, the methylation levels and patterns for Alu, HERV-E and HERV-K in the neutrophils from the SLE patients were not significantly different from the healthy controls. In addition, we further investigated whether there were any correlations between the intragenic LINE-1 and differential expressions of the neutrophils from the SLE patients using public arrays data. The upregulated genes in the neutrophils from the SLE patients were significantly associated with the genes containing LINE-1s compared with the healthy controls (P-value GSE27427 = 7.74 × 10(-3); odds ratio (OR) = 1.28). Interestingly, this association was mainly found among genes with antisense LINE-1s (P-value GSE27427 = 6.22 × 10(-3); OR = 1.38). Bioinformatics data suggest that LINE-1 hypomethylation may affect expression of the genes that may contribute to the pathogenesis of SLE. However, additional functional studies of these proposed genes are warranted to prove this hypothesis.
authors.affiliation: Center of Excellence in Immunology and Immune Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Patadon
authors.initials: P
authors.lastname: Sukapan
authors.affiliation: Medical Sciences Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Paramate
authors.initials: P
authors.lastname: Promnarate
authors.affiliation: Center of Excellence in Immunology and Immune Mediated Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yingyos
authors.initials: Y
authors.lastname: Avihingsanon
authors.affiliation: Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.affiliation: Center of Excellence in Immunology and Immune Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
mesh_terms: D000293:Adolescent; D000328:Adult; D020087:Alu Elements; D017209:Apoptosis; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D055815:Young Adult