Promoter Methylation and Expression Status of Cytotoxic T-Lymphocyte-Associated Antigen-4 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 CTLA4 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 CTLA4 gene in patients with lupus. Methods: Genomic DNA was isolated from 50 individuals’ blood samples with SLE and 50 control participants. CTLA4 gene polymorphisms analysis in polymorphic site, -318(CT) and +49(AG), was done by Tetra-ARMS-PCR. Methylation-specific polymerase chain reaction (MS-PCR) was used to estimate promoter hyper methylation of the CTLA4 gene. The present paper also analyzed CTLA4 mRNA levels in 30 blood samples from the intended participants, and healthy control by real-time PCR. Results: Changes in promoter methylation of CTLA4 gene were remarkably different in patients with lupus than healthy controls (OR= 0.48; 95% CI= 0.1959, 1.202; P-value= 0.005). However, gene expression level of CTLA4 was not statistically different in patients than the healthy control group. Conclusions: This epigenetic study gives us an overview of the role of CTLA4 promoter methylation in pathogenesis of SLE, which cause preventing its expression. As we know CTLA4 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).

Promoter Methylation and Expression Status of Cytotoxic T-Lymphocyte-Associated Antigen-4 Gene in Patients with Lupus Keywords:

Systemic lupus erythematous , CTLA4 gene , Polymorphism , promoter methylation , gene expression