Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus

被引：465

作者：

Javierre, Biola M. ^{[1
]}

Fernandez, Agustin F. ^{[2
]}

Richter, Julia ^{[3
]}

Al-Shahrour, Fatima ^{[4
,5
,6
]}

Martin-Subero, J. Ignacio ^{[3
]}

Rodriguez-Ubreva, Javier ^{[1
]}

Berdasco, Maria ^{[2
]}

Fraga, Mario F. ^{[2
]}

O'Hanlon, Terrance P. ^{[7
]}

Rider, Lisa G. ^{[7
]}

Jacinto, Filipe V. ^{[2
]}

Javier Lopez-Longo, F. ^{[8
]}

Dopazo, Joaquin ^{[4
,9
]}

Forn, Marta ^{[10
]}

Peinado, Miguel A. ^{[10
]}

Carreno, Luis ^{[8
]}

Sawalha, Amr H. ^{[11
,12
,13
]}

Harley, John B. ^{[11
,12
,13
]}

Siebert, Reiner ^{[3
]}

Esteller, Manel ^{[2
]}

Miller, Frederick W. ^{[7
]}

Ballestar, Esteban ^{[1
]}

机构：

[1] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Programme PEBC, Chromatin & Dis Grp, Barcelona 08907, Spain

[2] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Programme PEBC, Canc Epigenet Grp, Barcelona 08907, Spain

[3] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, D-24105 Kiel, Germany

[4] Ctr Invest Principe Felipe, Bioinformat Dept, Valencia 46012, Spain

[5] Broad Inst, Cambridge, MA 02142 USA

[6] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Brookline, MA 02115 USA

[7] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, HHS, Bethesda, MD 20892 USA

[8] Hosp Gen Gregorio Maranon, Div Rheumatol, Madrid 28007, Spain

[9] ISCIII Ctr Biomed Res Rare Dis, Valencia 46012, Spain

[10] IMPPC, Badalona 08916, Spain

[11] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA

[12] US Dept, Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA

[13] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA

来源：

GENOME RESEARCH | 2010年 / 20卷 / 02期

关键词：

T-CELLS; DEMETHYLATION; HYPOMETHYLATION; PROMOTER; DISEASE; INACTIVATION; LIPOCALIN-2; INTERFERON; EXPRESSION; RECEPTOR;

D O I：

10.1101/gr.100289.109

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：170 / 179

页数：10

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