The pituitary‐thyroid axis set point in women is uninfluenced by X chromosome inactivation pattern? A twin study

Abstract

The pituitary-thyroid axis (PTA) set point is determined by a combination of genetic and environmental factors. However, despite considerable efforts to characterize the background, the causative genes as well as environmental factors are not well established. Theoretically, as shown for autoimmune thyroid disease, the pattern of X chromosome inactivation (XCI) could offer a novel explanation for the observed variability of the PTA set point in women. To examine the impact of XCI pattern on the PTA set point, we studied whether within-cohort (n = 318 subjects) and within-twin pair (n = 159 pairs) differences in XCI are correlated with serum concentrations of thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4). X chromosome inactivation was determined by PCR analysis of a polymorphic CAG repeat in the first exon of the androgen receptor gene. Thyroid variables were measured using a solid-phase time-resolved fluoroimmunometric assay. Zygosity was established by DNA fingerprinting. In the overall study population (within cohort), no significant correlations were found between TSH [regression coefficient (β) = -0·28 (95% confidence intervals, -0·66 to 0·11), P = 0·158], FT3 [β = -0·25 (-0·85 to 0·34), P = 0·403], FT4 [β = 0·08 (-0·91 to 1·07), P = 0·876] and XCI pattern. Essentially similar results were found in the within-pair analysis. Controlling for confounders such as age, body mass index, smoking and zygosity did not change the findings. In a sample of female twins, we found no evidence of a relationship between XCI pattern and PTA set point.