Skewed X-chromosome inactivation (≥80%) was significantly more frequent in women with rheumatoid arthritis (34.2%) and autoimmune thyroid diseases (26%) compared to healthy controls (11.2%).
Case-Control (n=508)
Yes
Is skewed X-chromosome inactivation associated with rheumatoid arthritis and autoimmune thyroid diseases in females?
Skewed X-chromosome inactivation is significantly more common in females with rheumatoid arthritis and autoimmune thyroid diseases compared to healthy controls, suggesting a potential role in pathogenesis.
Absolute Event Rate: 34.2% vs 11.2%
p-value: p=<0.0001
INTRODUCTION: The majority of autoimmune diseases such as rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) are characterized by a striking female predominance superimposed on a predisposing genetic background. The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of several autoimmune diseases. METHODS: We examined XCI profiles of females affected with RA (n = 106), AITDs (n = 145) and age-matched healthy women (n = 257). XCI analysis was performed by enzymatic digestion of DNA with a methylation sensitive enzyme (HpaII) followed by PCR of a polymorphic CAG repeat in the androgen receptor (AR) gene. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X-chromosome. RESULTS: Skewed XCI was observed in 26 of the 76 informative RA patients (34.2%), 26 of the 100 informative AITDs patients (26%), and 19 of the 170 informative controls (11.2%) (P 90% inactivation of one allele, was present in 17 RA patients (22.4%), 14 AITDs patients (14.0%), and in only seven controls (4.1%, P 0.05). CONCLUSIONS: These results suggest a possible role for XCI mosaicism in the pathogenesis of RA and AITDs and may in part explain the female preponderance of these diseases.
Chabchoub et al. (Thu,) conducted a case-control in Rheumatoid arthritis and autoimmune thyroid diseases (n=508). Skewed X-chromosome inactivation vs. Healthy controls was evaluated on Skewed X-chromosome inactivation (≥80% inactivation of one allele) (p=<0.0001). Skewed X-chromosome inactivation (≥80%) was significantly more frequent in women with rheumatoid arthritis (34.2%) and autoimmune thyroid diseases (26%) compared to healthy controls (11.2%).