1. ¹Department of Molecular Biology and Genetics, Bilkent University, Faculty of Science, Ankara, Turkey
2. ²Department of Endocrinology and Metabolic Diseases, Ankara University, School of Medicine, Sihhiye, Ankara, Turkey
3. ³Gene Mapping Laboratory, Pediatric Hematology Unit, Department of Pediatrics, Hacettepe University, Medical Faculty, Sihhiye, Ankara, Turkey
4. ⁴Center for Human and Molecular Genetics, UMDNJ – New Jersey Medical School, Newark, NJ, USA

Correspondence: Professor T Ozcelik, Department of Molecular Biology and Genetics, Faculty of Science, B-242, Bilkent University, Bilkent, Ankara 06800, Turkey. Tel: +90 312 2902139; Fax: +90 312 2665097; E-mail: tozcelik@fen.bilkent.edu.tr

Received 11 November 2005; Revised 19 January 2006; Accepted 10 February 2006; Published online 5 April 2006.

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<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.