Browsing by Subject "Autoimmune diseases Genetic aspects."

Now showing 1 - 2 of 2

Open Access
Analysis of X chromosome inactivation in primary and secondary Sjogren syndrome
(2008) Kantar, Melda
Sjogren Syndrome is an autoimmune disease with one of the highest prevalences and unknown etiology. The majority of the patients (~90%) are female similar to several other autoimmune diseases. Based on this observation, a hypothesis was proposed stating that X chromosome inactivation (XCI) could be involved in female predisposition to autoimmunity. XCI is a physiological mechanism which takes place early in development resulting in the transcriptional silencing of one of the pair of X chromosomes at random in each cell. A significant deviation from a random distribution of two cell populations with paternal and maternal X chromosome inactive is called skewed XCI. Skewing in the dendritic cell population involved in tolerance induction in the thymus was proposed to cause escape of autoreactive lymphocytes and result in autoimmunity (Immunol Today, 19, 352-7, 1998). Skewed XCI was observed in scleroderma (Arth Rheum 52, 1564-70, 2005) and autoimmune thyroiditis (Eur J Hum Genet 14, 791-7, 2006). But this observation is not true for all autoimmune diseases. For example, the XCI profiles of primary biliary cirrhosis patients are similar to normal controls (Hepatol Res 37, Suppl 3, 384-8, 2007). The aim of this study is to determine the XCI profiles of patients diagnosed with primary Sjogren Syndrome, manifesting exocrinopathy or secondary Sjogren Syndrome displaying additional systemic features. DNA was isolated from the peripheric blood samples of 78 Sjogren syndrome patients and 160 controls. XCI profile was determined by the genotyping of a polymorphism in the androgen receptor (AR) gene. For this analysis, restriction enzyme HpaII was used which does not cut methylated regions. Analysis was done with Genescan Abi Prism 310 or 8% polyacrylamide gel electrophoresis and densitometric analysis. Extreme skewing (>90%) of XCI was observed in 3 (5.9%) patients and 3 controls (2.4%) samples (P = 0.3651). Our findings do not support a role for skewed XCI in Sjogren Syndrome.
Open Access
X chromosome inactivation in female predisposition to autoimmunity
(2008) Uz, Elif
The high female preponderance is thought to be important in identifying the etiological factors. Sex hormones, pregnancy related microchimerism, and environmental factors are investigated as likely candidates. Disturbed Xchromosome inactivation (XCI) is another candidate, which may contribute to the break-down of self-tolerance. In this study, we tested the hypothesis that “loss of mosaicism” for X-linked gene expression may contribute to autoimmune disease etiology. Therefore, XCI status of healthy individuals and patients diagnosed with scleroderma (SSc), autoimmune thyroiditis (AITDs), Sjogren’s syndrome (SICCA), and juvenile idiopathic arthritis (JIA) in the Turkish population were analyzed by genotyping the methylation status of a CAG polymorphism in the androgen receptor (AR) gene. Extremely skewed XCI was observed in a significant proportion of SSc (OR: 38.9; P<0.0001), AITDs (OR: 9.6; P<0.0001), and JIA (OR: 4.4; P=0.0022). Further genotyping of AITDs in Tunisian and SSc in the US population supported the initial observations (OR: 3.8; P=0.0046; OR: 3.8; P<0.0001) respectively. Analysis of rheumatoid arthritis (RA) in the Tunisian population suggests that extremely skewed XCI (OR: 6.7; P<0.0001) could be involved in disease pathogenesis. Moreover, pre-eclampsia, a disease in which autoimmunity may be important, skewed XCI was observed (OR; 11.7; P=0.0005). However, in SICCA random patterns of XCI was observed suggesting that extreme skewing is not a common feature of all female prevalent autoimmune disorders. In conclusion, our results suggest that extremely skewed XCI may be important factor in autoimmune disease pathogenesis.