Clinical Reviews in Allergy & Immunology

, Volume 34, Issue 3, pp 352–355

Skewed X-Chromosome Inactivation in Scleroderma

  • Elif Uz
  • Laurence S. Loubiere
  • Vijayakrishna K. Gadi
  • Zeynep Ozbalkan
  • Jeffrey Stewart
  • J. Lee Nelson
  • Tayfun Ozcelik
Article

DOI: 10.1007/s12016-007-8044-z

Cite this article as:
Uz, E., Loubiere, L.S., Gadi, V.K. et al. Clinic Rev Allerg Immunol (2008) 34: 352. doi:10.1007/s12016-007-8044-z

Abstract

Scleroderma is a female-prevalent autoimmune disease of unclear etiology. Two fundamental gender differences, skewed X-chromosome inactivation (XCI) and pregnancy-related microchimerism, have been implicated in scleroderma. We investigated the XCI patterns of female scleroderma patients and the parental origin of the inactive X chromosome in those patients having skewed XCI patterns (>80%). In addition, we investigated whether a correlation exists between XCI patterns and microchimerism in a well-characterized cohort. About 195 female scleroderma patients and 160 female controls were analyzed for the androgen receptor locus to assess XCI patterns in the DNA extracted from peripheral blood cells. Skewed XCI was observed in 67 (44.9%) of 149 informative patients and in 10 of 124 healthy controls (8.0%) [odds ratio (OR) = 9.3 (95% confidence interval (CI) 4.3–20.6, P < 0.0001)]. Extremely skewed XCI (>90%) was present in 44 of 149 patients (29.5%) but only in 3 of 124 controls (2.4%; OR = 16.9; 95% CI 4.8–70.4, P < 0.0001). Parental origin of the inactive X chromosome was investigated for ten patients for whom maternal DNA was informative, and the inactive X chromosome was of maternal origin in eight patients and of paternal origin in two patients. Skewed XCI mosaicism could be considered as an important risk factor in scleroderma.

Keywords

X-inactivationMicrochimerismMosaicismScleroderma

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Elif Uz
    • 1
  • Laurence S. Loubiere
    • 2
  • Vijayakrishna K. Gadi
    • 2
    • 3
  • Zeynep Ozbalkan
    • 4
  • Jeffrey Stewart
    • 5
  • J. Lee Nelson
    • 2
    • 3
  • Tayfun Ozcelik
    • 1
    • 6
  1. 1.Department of Molecular Biology and Genetics, Faculty of ScienceBilkent UniversityAnkaraTurkey
  2. 2.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  3. 3.Department of MedicineUniversity of WashingtonSeattleUSA
  4. 4.Rheumatology DepartmentAnkara Numune Education and Research HospitalAnkaraTurkey
  5. 5.Caldera PharmaceuticalsLos AlamosUSA
  6. 6.Institute for Materials Science and Nanotechnology (UNAM)Bilkent UniversityAnkaraTurkey