Skewed x-chromosome inactivation in juvenile idiopathic arthritis and rheumatoid arthritis

Abstract

There is a female predominance in most of the autoimmune diseases, and it is thought to play an important role in identifying the etiological factors. Sex hormones, microchimerism and environmental factors are thought to be responsible. Nowadays, it is proposed that a disturbance in mosaicism of females may cause autoimmune disease development. Recently, in our lab, an association between extremely skewed X-chromosome inactivation (XCI) patterns and female predisposition to autoimmunity was identified in Turkish population. In this study, we hypothesized that skewed XCI might play a role in the disease development of Juvenile idiopathic arthritis (JIA) in Turkish, and Rheumatoid Arthritis (RA) in French population. Therefore, XCI status of healthy individuals and patients diagnosed with JIA and RA were genotyped by analyzing androgen receptor (AR) locus by methylation sensitive HpaII digestion followed by PCR. Extremely skewed XCI was observed in a significant proportion of JIA (OR: 11.33; P=0.0008) in Turkish population, and RA (OR: 7.6; P=0.005) in French population. In conclusion, our results suggest that extremely skewed XCI may play an important role in autoimmune disease pathogenesis.