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

C. Selmi, C. A. Feghali-Bostwick, A. Lleo, S. A. Lombardi, M. De Santis, F. Cavaciocchi, L. Zammataro, M. M. Mitchell, Janine M LaSalle, T. Medsger, M. Eric Gershwin

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)253-262
Number of pages10
JournalClinical and Experimental Immunology
Volume169
Issue number3
DOIs
StatePublished - Sep 2012

Fingerprint

X-Linked Genes
Monozygotic Twins
Methylation
Lymphocytes
Genes
Dizygotic Twins
Sex Chromosomes
Connective Tissue Diseases
Surface Antigens
Immunoprecipitation
Epigenomics
Blood Cells
Oxidative Stress
Fibrosis
Transcription Factors
Cell Proliferation
Apoptosis
Inflammation
DNA

Keywords

  • Epigenetics
  • Genome-wide
  • MeDIP
  • Systemic autoimmunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma. / Selmi, C.; Feghali-Bostwick, C. A.; Lleo, A.; Lombardi, S. A.; De Santis, M.; Cavaciocchi, F.; Zammataro, L.; Mitchell, M. M.; LaSalle, Janine M; Medsger, T.; Gershwin, M. Eric.

In: Clinical and Experimental Immunology, Vol. 169, No. 3, 09.2012, p. 253-262.

Research output: Contribution to journalArticle

Selmi, C, Feghali-Bostwick, CA, Lleo, A, Lombardi, SA, De Santis, M, Cavaciocchi, F, Zammataro, L, Mitchell, MM, LaSalle, JM, Medsger, T & Gershwin, ME 2012, 'X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma', Clinical and Experimental Immunology, vol. 169, no. 3, pp. 253-262. https://doi.org/10.1111/j.1365-2249.2012.04621.x
Selmi, C. ; Feghali-Bostwick, C. A. ; Lleo, A. ; Lombardi, S. A. ; De Santis, M. ; Cavaciocchi, F. ; Zammataro, L. ; Mitchell, M. M. ; LaSalle, Janine M ; Medsger, T. ; Gershwin, M. Eric. / X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma. In: Clinical and Experimental Immunology. 2012 ; Vol. 169, No. 3. pp. 253-262.
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