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

• DOI: 10.1038/sj.ejhg.5201614
• Publication Date: 2006-04-05T04:57:56Z
• Authors: Tayfun Ozcelik; Elif Uz; Cemaliye B Akyerli; Sevgi Bagislar; Chigdem A Mustafa; Alptekin Gursoy; Nurten Akarsu; Gokce Toruner; Nuri Kamel; Sevim Gullu
• Keywords: Male; evidence based medicine; polymerase chain reaction; Biopsy; Female predisposition to autoimmunity; Autoimmunity; Pathogenesis; Gene locus; X Chromosome Inactivation; androgen receptor; DNA extraction; pathophysiology; familial disease; Priority journal; Genetics & Heredity; Hair follicle; X; 0303 health sciences; Type II site specific deoxyribonuclease; hair follicle; Hashimoto disease; Mosaicism; adult; pathogenesis; autoimmunity; article; Middle Aged; Graves Disease; Polymerase chain reaction; Pedigree; 3. Good health; Androgen receptor; female; priority journal; Graves disease; Female; Human; Adult; Biochemistry & Molecular Biology; gene locus; Major clinical study; Hashimoto Disease; Pathophysiology; Chromosomes; Article; Sex chromosome mosaicism; 03 medical and health sciences; blood cell; Cheek mucosa; Sex Factors; Humans; biopsy; controlled study; Genetic Predisposition to Disease; human; Human tissue; Chromosomes, Human, X; Thyroid gland; type II site specific deoxyribonuclease; thyroid gland; Blood cell; human cell; Genetic predisposition; cheek mucosa; major clinical study; human tissue; Autoimmune thyroid disease; Human cell; Evidence based medicine; sex chromosome mosaicism; Familial disease; X chromosome inactivation; genetic predisposition; Controlled study

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.