Preliminary evidence of a noncausal association between the X-chromosome inactivation pattern and thyroid autoimmunity: a twin study

• Published in: European journal of human genetics : EJHG Vol. 18; no. 2; pp. 254 - 257
• Main Authors: BRIX, Thomas Heiberg, HANSEN, Pia Skov, KYVIK, Kirsten Ohm, HEGEDÜS, Laszlo
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.02.2010
• Subjects: Adult; Androgens; Autoantibodies; Autoantibodies - blood; Autoimmunity; Biological and medical sciences; Cohort Studies; Denmark; Endocrinology; Epigenetics; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Health care; Humans; Iodide peroxidase; Iodide Peroxidase - immunology; Male; Medical genetics; Medical sciences; Middle Aged; Molecular and cellular biology; Pathogenesis; Patient Selection; Peroxidase; Polyglutamine; Short Report; Studies; Surveys and Questionnaires; Thyroid; Thyroid diseases; Thyroid Diseases - enzymology; Thyroid Diseases - genetics; Thyroid Diseases - immunology; Thyroid Gland - immunology; Thyrotropin - blood; Trinucleotide repeat diseases; Trinucleotide repeats; Twins; Twins, Dizygotic - genetics; Twins, Monozygotic - genetics; X Chromosome Inactivation - genetics; Young Adult; Denmark; Autoimmunity; Enzyme; Antibody; Autoantibody; thyroid autoimmunity; Thyroid gland; Inactivation; X-chromosome inactivation; Twin; thyroid autoantibodies; thyroid peroxidase antibodies; twins; Association; Peroxidases; Epigenetics; Genetics; Peroxidase; Oxidoreductases; X-Chromosome
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2009.156

An increased frequency of skewed X-chromosome inactivation (XCI) is found in clinically overt autoimmune thyroid disease (AITD) compared with controls. Whether skewed XCI is involved in the pathogenesis of autoantibodies to thyroid peroxidase (TPOAb) in euthyroid subjects is unknown. To examine the impact of XCI on the serum concentration of TPOAb, we studied whether within-cohort and within-twin-pair differences in XCI are associated with differences in serum concentrations of TPOAb. A total of 318 euthyroid female twin individuals distributed in 159 pairs were investigated. XCI was determined by PCR analysis of a polymorphic CAG repeat in the first exon of the androgen receptor gene. TPOAb concentrations were measured using a solid-phase time-resolved fluoroimmunometric assay. Overall (within cohort), there was a significant association between XCI and serum concentrations of TPOAb; regression coefficient (beta)=1.45 (95% confidence interval, 0.52-2.38), P=0.003. The association remained significant in the within-pair analysis; beta=1.74 (0.79-2.69), P<0.001. The relationship was nonsignificant within the 82 monozygotic pairs (beta=0.57 (-0.78-1.92), P=0.405), whereas the association was significant in the 77 dizygotic pairs (beta=2.17 (0.81-3.53), P=0.002). This preliminary finding of a significant association between TPOAb concentrations and XCI within cohort and within dizygotic but not within monozygotic twin pairs may indicate that XCI per se does not have a major role in the pathogenesis of TPOAb. More likely, XCI and TPOAb are influenced by shared genetic determinants.