Ankylos Spondylitis Research Paper

Ankylosing Spondylitis (AS) is a chronic and inflammatory rheumatologic disease which mainly affects the sacroiliac joints and spine, causing deformity of bones, which lead to disability of patients. Also, involves the peripheral joints and other extra-articular organs such as eyes, skin, and cardiovascular system. All these problems decrease the quality of AS patient's life (1, 2). It usually affects individuals from the early age and most of the patients develop the first symptoms before their third decade of life and, a few of them present the symptoms in the fourth decade of life (the peak age of onset is at 15-35 years). Prevalence rate ranges are varying between 0.1% and 2% in different populations. Men are more often affected than women, with an
approximate ratio 5/1 (3, 4). It has been shown that genetic and environmental factors play an important role in autoimmune diseases. AS is one of the rheumatologic diseases that suggest a large genetic contribution to the risk of disease (5). It is showed that the Bcl11b is a novel candidate gene that might contribute to the AS disease (6). Bcl11b gene located on human chromosome 14q32.2 and plays an important role in T-cell development, differentiation, and proliferation, and over-expression of this gene has been associated with T-cell malignancies because this gene is specifically expressed in T cells. This gene has numerous roles that inhibit the apoptosis (7). Epigenetics can be described as a process that affects the inheritance of genes without changes in DNA base sequences. DNA methylation is an important epigenetic modification.
The major role of the DNA methylation to inhibit the gene expression is attracting proteins, which contain a methylated DNA binding domain (MBD). MBD-containing proteins provide connections between methylated DNA and histone modifications that induce heterochromatin and suppress the gene expression. It is shown that the DNA methylation has been associated with autoimmunity disorders with the DNA methylation inhibitor 5-azacytidine, which induce autoimmune disease in experimental animals (8). DNA methylation of CpG islands in the promoter region leads to epigenetic gene inactivation by inducing heterochromatin formation (9). Due to the important role of Bcl11b, the first aim was to investigate whether the expression level is associated with susceptibility and clinical features of AS. The next aim was to investigate whether the expression level is related to the DNA methylation of this gene. So, we examined the relationship between DNA methylation of the Bcl11b gene and its gene expression in the AS patients. Furthermore, we evaluate methylation status of CpG sites in the promoter of Bcl11b gene and assess the effect of that on transcriptional level of this
gene.