Extremely skewed x-chromosome inactivation in juvenile idiopathic arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with female predominance and an incidence between 7-21/100,000. There are several explanations for the reason of disease development, such as environmental factors that trigger autoimmunity and genetic basis. The genetic basis of JIA is not well defined. It rarely manifests familial recurrence. But the monozygotic twin data suggest that there is a considerable genetic basis, which is likely to involve multiple epigenetic events. It was 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. Since JIA is thought to have an autoimmune etiology, we hypothesized that skewed XCI might play a role in the disease development. To determine XCI status, androgen receptor locus was analyzed by methylation sensitive Hpa II digestion followed by PCR by using of 72 female patients diagnosed with JIA and 183 female controls, which comprised of newborns (n=91) and children with no history of an autoimmune condition (n=92). A male control (46, XY) was used for complete digestion in the analysis of XCI pattern. We expect to see an association between extremely skewed XCI and female predisposition to JIA.