epigenetics: monozygotic twin discordance in systemic lupus erythematosus

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.. *Changes in the pattern of DNA methylation associate with twin

discordance in systemic lupus erythematosus*

re BM, Fernandez AF, Richter J, Al-Shahrour F, -Subero JI,

-Ubreva J, Berdasco M, Fraga MF, O'Hanlon TP, Rider LG, Jacinto

FV, -Longo FJ, Dopazo J, Forn M, Peinado MA, Carreño L, Sawalha AH,

Harley JB, Siebert R, Esteller M, FW, Ballestar E.

Chromatin and Disease Group, Cancer Epigenetics and Biology Programme

(PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet

de Llobregat, Barcelona 08907, Spain;

Genome Res. 2009 Dec 22. [Epub ahead of print]

http://genome.cshlp.org/content/20/2/170.long

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.