Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity
Author
Ozcelik, T.
Uz, E.
Akyerli, C. B.
Bagislar, S.
Mustafa, C. A.
Gursoy, A.
Akarsu, N.
Toruner, G.
Kamel, N.
Gullu, S.
Date
2006Source Title
European Journal of Human Genetics
Print ISSN
1018-4813
Publisher
Nature Publishing Group
Volume
14
Issue
6
Pages
791 - 797
Language
English
Type
ArticleItem Usage Stats
154
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Abstract
The etiologic factors in the development of autoimmune thyroid diseases (AITDs) are not fully understood. We investigated the role of skewed X-chromosome inactivation (XCI) mosaicism in female predisposition to AITDs. One hundred and ten female AITDs patients (81 Hashimoto's thyroiditis (HT), 29 Graves' disease (GD)), and 160 female controls were analyzed for the androgen receptor locus by the HpaII/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. In addition, thyroid biopsy, buccal mucosa, and hair follicle specimens were obtained from five patients whose blood revealed an extremely skewed pattern of XCI, and the analysis was repeated. Skewed XCI was observed in DNA from peripheral blood cells in 28 of 83 informative patients (34%) as compared with 10 of 124 informative controls (8% P<0.0001). Extreme skewing was present in 16 patients (19%), but only in three controls (2.4% P<60;0.0001). The buccal mucosa, and although less marked, the thyroid specimens also showed skewing. Analysis of two familial cases showed that only the affected individuals demonstrate skewed XCI patterns. Based on these results, skewed XCI mosaicism may play a significant role in the pathogenesis of AITDs.
Keywords
Autoimmune thyroid diseaseFemale predisposition to autoimmunity
X chromosome inactivation
Androgen receptor
Type II site specific deoxyribonuclease
Adult
Article
Autoimmunity
Biopsy
Blood cell
Cheek mucosa
Controlled study
DNA extraction
Evidence based medicine
Familial disease
Female
Gene locus
Genetic predisposition
Graves disease
Hair follicle
Hashimoto disease
Human
Human cell
Human tissue
Major clinical study
Pathogenesis
Pathophysiology
Polymerase chain reaction
Priority journal
Sex chromosome mosaicism
Thyroid gland
X chromosome inactivation
Adult
Chromosomes, Human, X
Genetic Predisposition to Disease
Graves Disease
Hashimoto Disease
Humans
Male
Middle Aged
Mosaicism
Pedigree
Sex Factors
X Chromosome Inactivation
Permalink
http://hdl.handle.net/11693/23788Published Version (Please cite this version)
http://dx.doi.org/10.1038/sj.ejhg.5201614Collections
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