Article

Clinical Reviews in Allergy & Immunology

, Volume 34, Issue 3, pp 352-355

First online:

Skewed X-Chromosome Inactivation in Scleroderma

  • Elif UzAffiliated withDepartment of Molecular Biology and Genetics, Faculty of Science, Bilkent University
  • , Laurence S. LoubiereAffiliated withClinical Research Division, Fred Hutchinson Cancer Research Center
  • , Vijayakrishna K. GadiAffiliated withClinical Research Division, Fred Hutchinson Cancer Research CenterDepartment of Medicine, University of Washington
  • , Zeynep OzbalkanAffiliated withRheumatology Department, Ankara Numune Education and Research Hospital
  • , Jeffrey StewartAffiliated withCaldera Pharmaceuticals
  • , J. Lee NelsonAffiliated withClinical Research Division, Fred Hutchinson Cancer Research CenterDepartment of Medicine, University of Washington
  • , Tayfun OzcelikAffiliated withDepartment of Molecular Biology and Genetics, Faculty of Science, Bilkent UniversityInstitute for Materials Science and Nanotechnology (UNAM), Bilkent University Email author 

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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-inactivation Microchimerism Mosaicism Scleroderma