ORIGINAL ARTICLE

X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma

  1. C. Selmi1,4,*,
  2. C. A. Feghali-Bostwick3,
  3. A. Lleo1,5,
  4. S. A. Lombardi4,
  5. M. De Santis4,
  6. F. Cavaciocchi4,
  7. L. Zammataro4,
  8. M. M. Mitchell2,
  9. J. M. LaSalle2,
  10. T. Medsger Jr3,
  11. M. E. Gershwin1

Article first published online: 2 AUG 2012

DOI: 10.1111/j.1365-2249.2012.04621.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 169, Issue 3, pages 253–262, September 2012

Additional Information

How to Cite

Selmi, C., Feghali-Bostwick, C. A., Lleo, A., Lombardi, S. A., De Santis, M., Cavaciocchi, F., Zammataro, L., Mitchell, M. M., LaSalle, J. M., Medsger Jr, T. and Gershwin, M. E. (2012), X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma. Clinical & Experimental Immunology, 169: 253–262. doi: 10.1111/j.1365-2249.2012.04621.x

Author Information

  1. 1

    Division of Rheumatology, Allergy, and Clinical Immunology

  2. 2

    Medical Microbiology and Immunology, Genome Center and MIND Institute, University of California, Davis, CA

  3. 3

    Scleroderma Center, Department of Medicine, University of Pittsburgh, PA, USA

  4. 4

    Clinical Immunology

  5. 5

    Center for Autoimmune Liver Diseases, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy

*C. Selmi, Clinical Immunology, IRCCS Istituto Clinico Humanitas, via A. Manzoni 56, 20089 Rozzano, Milan, Italy. E-mail: carlo.selmi@unimi.it

Publication History

  1. Issue published online: 2 AUG 2012
  2. Article first published online: 2 AUG 2012
  3. Accepted manuscript online: 14 JUN 2012 07:04AM EST
  4. Accepted for publication 16 May 2012

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Keywords:

  • epigenetics;
  • genome-wide;
  • MeDIP;
  • systemic autoimmunity

Summary

Scleroderma (SSc) is a rare connective tissue disease characterized by fibrosis, microvasculopathy and autoimmune features. The role of genetics is limited in SSc, as suggested by similar concordance rates in monozygotic and dizygotic twin pairs, while environmental factors may act through epigenetic changes, as demonstrated for specific genes. Further, sex chromosome changes have been reported in SSc and may explain the female preponderance. In the present study we compared the methylation profile of all X chromosome genes in peripheral blood mononuclear cells from monozygotic twins discordant (n = 7) and concordant (n = 1) for SSc. Methylated DNA immunoprecipitations from each discordant twin pair were hybridized to a custom-designed array included 998 sites encompassing promoters of all X chromosome genes and randomly chosen autosomal genes. Biostatistical tools identified sites with an elevated probability to be consistently hypermethylated (n = 18) or hypomethylated (n = 25) in affected twins. Identified genes include transcription factors (ARX, HSFX1, ZBED1, ZNF41) and surface antigens (IL1RAPL2, PGRMC1), and pathway analysis suggests their involvement in cell proliferation (PGK1, SMS, UTP14A, SSR4), apoptosis (MTM1), inflammation (ARAF) and oxidative stress (ENOX2). In conclusion, we propose that X chromosome genes with different methylation profiles in monozygotic twin pairs may constitute candidates for SSc susceptibility.

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