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Part I. Genetics and Autoimmunity |
Thyroid EpigeneticsX Chromosome Inactivation in Patients with Autoimmune Thyroid Disease
XIAOMING YINa,
RAUF LATIFa,
YARON TOMERb AND
TERRY F. DAVIESa
a Department of Medicine, Mount Sinai School of Medicine, and James J. Peters Veterans Affairs Medical Center, New York, New York, USA b University of Cincinnati, Cincinnati, Ohio, USA
Key Words: epigenetics • X chromosome inactivation • autoimmune thyroid disease • Graves' disease • Hashimoto's thyroiditis
Address for correspondence: Dr. T.F. Davies, Room 2F-26, Bronx VAMC Research Division, 130 West Kingsbridge Rd., New York, NY 10468, USA. Voice: 1-212-241-7975; fax: 1-212-428-6748. terry.davies{at}mssm.edu
The autoimmune thyroid diseases (AITDs) are female-predominant diseases with a ratio of approximately seven females to each male. X chromosome inactivation (XCI), an epigenetic phenomenon, has been suggested to be skewed in many such female patients with AITD. We analyzed female genomic DNA from 87 patients with Graves' disease (GD), 47 patients with Hashimoto's thyroiditis (HT), and 69 healthy controls. Using an XCI assay based on Hpa II digestion and PCR and DNA sequencing, we found skewed heterozygous XCI ( 80%) in 20 of 70 GD patients (28.6%) and 11 of 43 HT patients (25.6%), giving a total of 31 of 113 AITD patients (27.4%) with skewed XCI. In contrast, only 5 of 58 healthy controls had skewed XCI (8.6%). Statistical analysis confirmed that XCI skewing was significantly associated with AITD (P = 0.004, OR = 4.0), demonstrating that the degree of XCI is an important contributor to the increased risk of females in developing AITD.
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