Analysis of CTLA۴ Gene Methylation and Its Expression In Individuals With Drug Addiction

Substance abuse is known as a relapsing and chronic disorder. Drug abuse has a significant role in the dopaminergic system in which dopamine is an important neurotransmitter.  Binding dopamine and dopamine receptors could activate major intracellular signalling through protein kinase A (PKA). Activation of intracellular signalling such CREB affect gene expression of some genes. As dopamine and dopaminergic system have an important regulation role in the inhibition of immune system we analysed the effects of drug addiction on the DNA methylation and expression of cytotoxic T-lymphocyte antigen ۴ (CTLA-۴). We evaluate promoter methylation and mRNA expression of CTLA-۴ in individual with drug addiction. DNA was extracted from blood of ۷۴ patients with drug addiction and ۵۹ healthy controls. Methylation of CTLA-۴ promoter was assessed using a methylation-specific PCR technique. In addition the expression level of CTLA-۴ was also indicated in ۱۷ individuals with drug addiction and ۱۸ people of controls. Although Promoter Methylation of CTLA-۴ was not significantly different between these two groups, expression of CTLA-۴ was remarkably different among them. We observed that each one of the drugs can increase the mRNA expression of CTLA_۴. Therefore, we suggest that further research for other epigenetic factors is required to detect the underlying cause of changing gene expression.

Keywords:

CTLA-۴ , Drug addiction , gene expression , Methylation-Specific PCR (MSP) , promoter methylation