TY - JOUR
T1 - Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity
AU - Ozcelik, Tayfun
AU - Uz, Elif
AU - Akyerli, Cemaliye B.
AU - Bagislar, Sevgi
AU - Mustafa, Chigdem A.
AU - Gursoy, Alptekin
AU - Akarsu, Nurten
AU - Toruner, Gokce
AU - Kamel, Nuri
AU - Gullu, Sevim
N1 - Funding Information:
We thank Margaret Sands, Iclal Ozcelik, and Ozlen Konu for critical reading of the manuscript. This study was supported by grants from the Scientific and Technical Research Council of Turkey – TUBITAK-SBAG 2513, International Centre for Genetic Engineering and Biotechnology – ICGEB-CRP/TUR04-01, and Bilkent University Research Fund (to Dr Ozcelik).
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
KW - Autoimmune thyroid disease
KW - Female predisposition to autoimmunity
KW - X chromosome inactivation
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U2 - 10.1038/sj.ejhg.5201614
DO - 10.1038/sj.ejhg.5201614
M3 - Article
C2 - 16596118
AN - SCOPUS:33744503390
SN - 1018-4813
VL - 14
SP - 791
EP - 797
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -