Abstract
Background: A skewed X chromosome inactivation (XCI) pattern has been found associated with clinically overt autoimmune thyroid disease (AITD) in females. Whether XCI is involved in the pathogenesis of subclinical AITD – autoantibodies to thyroid peroxidase (TPOAb) in euthyroid subjects – is unknown.
Objective and design: In order to examine the impact of XCI on the development of TPOAb in euthyroid subjects, we studied whether within cohort and within twin pair differences in XCI are associated with differences in serum concentrations of TPOAb. Subjects: 318 euthyroid female twin individuals (median age 36 years, range 17-57) distributed in 158 same-sex pairs.
Methods: 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.
Results: Overall (within cohort, n=318) there was a statistically significant association between XCI and serum concentrations of TPOAb; regression coefficient (?) = 0.99 (95% confidence interval, 0.02-1.96), p = 0.045. Controlling for potential confounders such as age, serum TSH, zygosity and smoking did not significantly change this. The association remained statistically significant in the within pair analysis (n=158 pairs); ? = 1.63 (0.67-2.58), p = 0.001. Stratification according to zygosity had a major impact on the results in the within pair analysis. The relationship was non-significant within the 82 monozygotic (MZ) pairs (? = 0.05 (-0.86-1.86), p = 0.465) whereas the association was significant in the 77 dizygotic (DZ) pairs (? = 2.00 (0.63-3.37), p = 0.005).
Conclusion: The finding of an association between TPOAb concentrations and XCI both within cohort and within twin pairs suggest a possible role of XCI in the aetiology of subclinical AITD. Moreover, since the association disappeared within MZ but not within DZ pairs, genes may be importantly involved in this relationship.