Skewed X-chromosome inactivation in scleroderma

Date
2008
Authors
Uz, E.
Loubiere, L. S.
Gadi, V. K.
Ozbalkan, Z.
Stewart, J.
Nelson, J. L.
Ozcelik, T.
Advisor
Instructor
Source Title
Clinical Reviews in Allergy and Immunology
Print ISSN
1080-0549
Electronic ISSN
Publisher
Springer New York
Volume
34
Issue
3
Pages
352 - 355
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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.

Course
Other identifiers
Book Title
Keywords
Microchimerism, Mosaicism, Scleroderma, X-inactivation, Androgen receptor, DNA, Article, Clinical feature, Controlled study, DNA extraction, DNA polymorphism, Female, Gene locus, Heterozygosity, Human, Major clinical study, Microchimerism, Risk factor, Scleroderma, X chromosome inactivation, Chimerism, Humans, Scleroderma, Systemic, X Chromosome Inactivation
Citation
Published Version (Please cite this version)