Abstract
Context: Simple goitre (SG) comprises non-toxic diffuse (DG) and nodular goitre (NG). In non-endemic goitre areas the ratio of females to males may exceed 10:1, indicating that gender and/or sex hormones may play a role in the aetiology of SG in these areas. As suggested for autoimmune thyroid disease, X chromosome inactivation (XCI) and resultant tissue chimerism could offer an explanation for the female preponderance of SG. Aim: To examine whether skewed XCI is associated with SG.
Design and participants: We first conducted a classical case-control study of female twin individuals with (n=71) and without (n=142) SG, and then a case-control study of female twin pairs discordant for SG (n=48 pairs).
Methods: The XCI pattern was determined by PCR analysis of a polymorphic CAG repeat in the first exon of the androgen receptor gene. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X chromosome.
Main outcome measures: The prevalence of skewed XCI.
Results: The frequency of skewed XCI in female twins with SG, DG and NG was 11% (8/71), 13% (6/46) and 8% (2/25), respectively, which was not significantly different from the prevalences in the corresponding control populations, 14% (20/142, p = 0.56), 14% (13/92, p = 1.00) and 14% (7/50, p = 0.71), respectively. Similar results were obtained when comparing the prevalence of skewed XCI in twin pairs discordant for SG (48 pairs), DG (30 pairs) and NG (18 pairs).
Conclusion: We found similar prevalences of skewed XCI in females with and without SG. Moreover, the frequency of skewed XCI was also similar when comparing the twins with SG with their healthy co-twins. These observations indicate that XCI is neither involved in the aetiology nor the female preponderance of SG.