Promoter Methylation and Expression Status of Cytotoxic T-Lymphocyte-Associated Antigen-۴ Gene in Patients with Lupus

Objectives: Systemic lupus erythematous (SLE) is an autoimmune disease with both genetic susceptibility and epigenetic modifications. Autoantibodies directly contribute to the destruction of some organs such as kidneys, joints, skin, lungs, central nervous system, and blood-forming (hematopoietic) system. The CTLA۴ plays an important role in inhibition of the activity of T cells and preventing autoimmune disorders, for example; the lupus. We analyzed the promoter methylation, polymorphism, and expression status in CTLA۴ gene in patients with lupus. Methods: Genomic DNA was isolated from ۵۰ individuals’ blood samples with SLE and ۵۰ control participants. CTLA۴ gene polymorphisms analysis in polymorphic site, -۳۱۸(CT) and +۴۹(AG), was done by Tetra-ARMS-PCR. Methylation-specific polymerase chain reaction (MS-PCR) was used to estimate promoter hyper methylation of the CTLA۴ gene. The present paper also analyzed CTLA۴ mRNA levels in ۳۰ blood samples from the intended participants, and healthy control by real-time PCR. Results: Changes in promoter methylation of CTLA۴ gene were remarkably different in patients with lupus than healthy controls (OR= ۰.۴۸; ۹۵% CI= ۰.۱۹۵۹, ۱.۲۰۲; P-value= ۰.۰۰۵). However, gene expression level of CTLA۴ was not statistically different in patients than the healthy control group. Conclusions: This epigenetic study gives us an overview of the role of CTLA۴ promoter methylation in pathogenesis of SLE, which cause preventing its expression. As we know CTLA۴ has the role in immune regulation and downregulates immune responses. In the future a comprehensive understanding of the epigenetic mechanisms contributing to SLE will likely enable development of new therapeutic agents and strategies that target the dysregulated genes or correct the aberrant epigenetic modifications (Epigenetic therapies for SLE).

کلیدواژه ها:

Systemic lupus erythematous ، CTLA۴ gene ، Polymorphism ، promoter methylation ، gene expression