Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases
Citations Over TimeTop 15% of 2009 papers
Abstract
Abstract 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 ( Hpa II) 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 < 0.0001; P = 0.0015, respectively). More importantly, extremely skewed XCI, defined as > 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 < 0.0001; P = 0.0034, respectively). Stratifying RA patients according to laboratory profiles (rheumatoid factor and anti-citrullinated protein antibodies), clinical manifestations (erosive disease and nodules) and the presence of others autoimmune diseases did not reveal any statistical significance ( 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.
Related Papers
- Rheumatoid arthritis and astercantha longifolia.(1999)
- Susquehanna Chorale Spring Concert "Roots and Wings"(2017)
- → DETERMINING QUALITY REQUIREMENTS AT THE UNIVERSITIES TO IMPROVE THE QUALITY OF EDUCATION(2018)
- → ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ(2024)