Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity

Date
2006
Authors
Ozcelik, T.
Uz, E.
Akyerli, C. B.
Bagislar, S.
Mustafa, C. A.
Gursoy, A.
Akarsu, N.
Toruner, G.
Kamel, N.
Gullu, S.
Advisor
Instructor
Source Title
European Journal of Human Genetics
Print ISSN
1018-4813
Electronic ISSN
Publisher
Nature Publishing Group
Volume
14
Issue
6
Pages
791 - 797
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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.

Course
Other identifiers
Book Title
Keywords
Autoimmune thyroid disease, Female 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
Citation
Published Version (Please cite this version)