RT Journal
A1 Javierre, Biola M.
A1 Fernandez, Agustin F.
A1 Richter, Julia
A1 Al-Shahrour, Fatima
A1 Martin-Subero, J. Ignacio
A1 Rodriguez-Ubreva, Javier
A1 Berdasco, Maria
A1 Fraga, Mario F.
A1 O'Hanlon, Terrance P.
A1 Rider, Lisa G.
A1 Jacinto, Filipe V.
A1 Lopez-Longo, F. Javier
A1 Dopazo, Joaquin
A1 Forn, Marta
A1 Peinado, Miguel A.
A1 Carreño, Luis
A1 Sawalha, Amr H.
A1 Harley, John B.
A1 Siebert, Reiner
A1 Esteller, Manel
A1 Miller, Frederick W.
A1 Ballestar, Esteban
T1 Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus
JF Genome Research 
JO Genome Research 
YR 2010 
FD February 01 
VO 20 
IS 2 
SP 170 
OP 179 
DO 10.1101/gr.100289.109 
UL http://genome.cshlp.org/content/20/2/170.abstract 
AB Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.