Skewed X Chromosome Inactivation In Blood Cells Of Women With Scleroderma

Autor: Meral Calguneri, Cemaliye B Akyerli, Hte Ozer, Sevgi Bagislar, Sule Yavuz, Sedat Kiraz, Zeynep Ozbalkan, Tayfun Ozcelik, AM Birlik
Přispěvatelé: İç Hastalıkları, Çukurova Üniversitesi
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Pathogenesis
Scleroderma
Disease predisposition
Pregnancy
Azathioprine
Autoimmune disease
Immunology and Allergy
Pharmacology (medical)
X chromosome
Priority journal
Hair follicle
DNA methylation
medicine.diagnostic_test
integumentary system
Penicillamine
Chloroquine
Microchimerism
Middle Aged
Connective tissue disease
Polymerase chain reaction
Androgen receptor
Immunosuppressive agent
Systemic sclerosis
Female
Immunosuppressive Agents
Human
Adult
Immunology
Major clinical study
Biology
Y chromosome
Article
X-inactivation
Sex chromosome mosaicism
Cheek mucosa
Systemic lupus erythematosus
Rheumatology
Autoantigen
Dosage Compensation
Genetic
Skin biopsy
medicine
Humans
Mycophenolic acid
Human tissue
Rheumatoid arthritis
Cyclophosphamide
Skewed X-inactivation
Aged
Chromosomes
Human
X
Scleroderma
Systemic
Blood cell
DNA
medicine.disease
Immunosuppressive treatment
Methotrexate
X chromosome inactivation
Controlled study
Zdroj: Arthritis and Rheumatism
Popis: PubMedID: 15880831 Objective. Scleroderma (SSc) is an autoimmune disease of unknown etiology. The disease is 3-8 times more frequent in women than in men. The role of X chromosome inactivation (XCI) in the predisposition of women to autoimmunity has been questioned. Until now this has not been illustrated experimentally. This study was undertaken to test the hypothesis that disturbances in XCI mosaicism may be involved in the pathogenesis of the disease in female patients with SSc. Methods. Seventy female SSc patients and 160 female controls were analyzed for the androgen receptor locus by the Hpa II/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. Furthermore, skin biopsy samples were obtained from 5 patients whose blood revealed an extremely skewed pattern of XCI, and the analysis repeated. Since microchimerism in SSc was reported, Y chromosome sequences were investigated in all samples. Results. Skewed XCI was observed in DNA from peripheral blood cells in 35 of 55 informative patients (64%), as compared with 10 of 124 informative controls (8%) (P < 0.0001). Extreme skewing was present in 27 of the patient group (49%), as compared with only 3 of the controls (2.4%) (P < 0.0001). However, XCI was random in all skin biopsy samples. The potential contribution of microchimerism to the random XCI pattern is highly unlikely based on the medical histories of the patients. Conclusion. Skewed XCI mosaicism may play a significant role in the pathogenesis of SSc. © 2005, American College of Rheumatology.
Databáze: OpenAIRE
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