Analysis of CTLA4 Gene Methylation and Its Expression In Individuals With Drug Addiction

Document Type : Original Article

Authors

1 Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran

2 Clinical Toxicologist, Emergency Medicine Department, Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

Abstract

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 4 (CTLA-4). We evaluate promoter methylation and mRNA expression of CTLA-4 in individual with drug addiction. DNA was extracted from blood of 74 patients with drug addiction and 59 healthy controls. Methylation of CTLA-4 promoter was assessed using a methylation-specific PCR technique. In addition the expression level of CTLA-4 was also indicated in 17 individuals with drug addiction and 18 people of controls. Although Promoter Methylation of CTLA-4 was not significantly different between these two groups, expression of CTLA-4 was remarkably different among them. We observed that each one of the drugs can increase the mRNA expression of CTLA_4. Therefore, we suggest that further research for other epigenetic factors is required to detect the underlying cause of changing gene expression.

Keywords

References

Abreu-Villaça, Y., Manhães, A.C., Krahe,T.E., Filgueiras,C.C, and Ribeiro-Carvalho, A. (2017). Tobacco and Alcohol Use during Adolescence: Interactive Mechanisms in Animal Models. Biochemical Pharmacology, 144, 1–17. https://doi.org/10.1016/j.bcp.2017.06.113.
Basu, S., and Sarathi Dasgupta, P. (2000). Dopamine, a Neurotransmitter, Influences the Immune System. Journal of Neuroimmunology, 102 (2),113–24. https://doi.org/10.1016/S0165-5728(99)00176-9.
Birtwistle, J., Baldwin, D. (1998). Role of dopamine in schizophrenia and Parkinson's disease. British  journal of nursing, ,7,832-4.
Brunet, J.F., Denizot, F., Luciani, M., Roux-Dosseto, M., Suzan, M., Mattei, M.G., and et al. (1987). A new member of the immunoglobulin superfamily--CTLA-4. Nature,328,267-70.
Hoi-Hung, C., Lee,T., Rennert, O.M, and Chan, W.Y. (2009). DNA Methylation of Cancer Genome. Birth Defects Research Part C: Embryo Today: Reviews, 87 (4),335–50. https://doi.org/10.1002/bdrc.20163.
Gaetano Di, C., and Bassareo, V. (2007). Reward System and Addiction: What Dopamine Does and Doesn’t Do. Current Opinion in Pharmacology, 7 (1),69–76. https://doi.org/10.1016/j.coph.2006.11.003.
Colucci, F., Bergman, M.L., Penha-Gonçalves, C., Cilio, C.M., and Holmberg, D. (1997). Apoptosis Resistance of Nonobese Diabetic Peripheral Lymphocytes Linked to the Idd5 Diabetes Susceptibility Region. Proceedings of the National Academy of Sciences of the United States of America, 94 (16), 8670–74. https://doi.org/10.1073/pnas.94.16.8670.
Doyle, H. A., and Mamula, M.J. (2001). Post-Translational Protein Modifications in Antigen Recognition and Autoimmunity. Trends in Immunology, 22 (8), 443–49. https://doi.org/10.1016/S1471-4906(01)01976-7.
Fiserová, A., Miroslav, S., Kuldová, M., Kovárů, H., Páv, M., Vannucci, L., and Pospísil, M. (2002). Effects of D2-Dopamine and Alpha-Adrenoceptor Antagonists in Stress Induced Changes on Immune Responsiveness of Mice. Journal of Neuroimmunology, 130 (1–2), 55–65. http://www.ncbi.nlm.nih.gov/pubmed/12225888.
Vasile, H., Yamada, K., Hefco, A., Hritcu, L., Tiron, A., Olariu, A., and Nabeshima, T. (2003). Effects of Nicotine on Memory Impairment Induced by Blockade of Muscarinic, Nicotinic and Dopamine D2 Receptors in Rats. European Journal of Pharmacology, 474 (2–3), 227–32. https://doi.org/10.1016/S0014-2999(03)02034-X.
Kordi-Tamandani, D.M., Tajoddini, S., and Salimi, F. (2015). Promoter Methylation and BDNF and DAT1 Gene Expression Profiles in Patients with Drug Addiction. Pathobiology, 82 (2), 94–99. https://doi.org/10.1159/000430465.
Kreek, M. J., Levran, O., Reed, B., Schlussman, S.D., Zhou, Y., and Butelman, E.R. (2012) Opiate Addiction and Cocaine Addiction : Underlying Molecular Neurobiology and Genetics. J Clin Invest, 122 (10), 3387- 3393 https://doi.org/10.1172/JCI60390.cocaine.
Liu, J. C., Baker, R.E., Chow, W., Sun, C.K., and Elsholtz, H.p. (2005). Epigenetic Mechanisms in the Dopamine D2 Receptor-Dependent Inhibition of the Prolactin Gene. Molecular Endocrinology, 19 (7),1904–17. https://doi.org/10.1210/me.2004-0111.
Mitsuiki, N., Schwab, C., and Grimbacher, B. (2018). What did we learn from CTLA‐4 insufficiency on the human immune system? Immunological Reviews, 287,33–49.
Muller, N., Ackenheil, M., Hofschuster, E., Mempel, W., Eckstein, R. (1993). Cellular immunity, HLA-class I antigens, and family history of psychiatric disorder in endogenous psychoses. Psychiatry research, 48,201-17.
Perez, A., Guan,L., and Sutherland, K., Cao1, C. (2016). Immune System and Parkinson’s Disease. Arch Med, 8 (2),1–6.
Yihua, Q., Peng, Y., and Wang, J. (1996). Immunoregulatory Role of Neurotransmitters. Advances in Neuroimmunology, 6 (3),223–31. https://doi.org/10.1016/S0960-5428(96)00018-6.
Robison, A..J., and Nestler, E.J. (2011). Transcriptional and Epigenetic Mechanisms of Addiction. Nature Reviews Neuroscience, 12 (11), 623–37. https://doi.org/10.1038/nrn3111.
Smith, R. J., and Laiks, L.S. (2017). Behavioral and Neural Mechanisms Underlying Habitual and Compulsive Drug Seeking. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 87, 11-21.https://doi.org/10.1016/j.pnpbp.2017.09.003.
Kordi Tamandani, D. M., Hashemi, M., and Shafiepour, S. (2013). Analysis of Cytotoxic T-Lymphocyte-Associated Antigen-4 and MMP-9 Genes’ Methylation and Their Expression Profiles with Risk of Non-Alcoholic Fatty Liver Disease. Indian Journal of Human Genetics, 19 (2),144–49. https://doi.org/10.4103/0971-6866.116106.
Vandaele, Y., and Janak, P.H. (2017). Defining the Place of Habit in Substance Use Disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 87, 22-32. https://doi.org/10.1016/j.pnpbp.2017.06.029.
Vassoler, F. M., and Sadri-Vakili, G. (2014). Mechanisms of Transgenerational Inheritance of Addictive-like Behaviors. Neuroscience, 264,198–206. https://doi.org/10.1016/j.neuroscience.2013.07.064.
Volkow, N. D., Fowler, J.S., Wang, G.J., and. Swanson, J.M. (2004). Dopamine in Drug Abuse and Addiction: Results from Imaging Studies and Treatment Implications. Molecular Psychiatry, 9 (6),557–69. https://doi.org/10.1038/sj.mp.4001507.
Wang, Y., and Leung, F.C. (2004). An Evaluation of New Criteria for CpG Islands in the Human Genome as Gene Markers. Bioinformatics, 20 (7),1170–77. https://doi.org/10.1093/bioinformatics/bth059.
Zhou, Z., Yuan, Q., Mash, D.C., and Goldman, D. (2011). Substance-Specific and Shared Transcription and Epigenetic Changes in the Human Hippocampus Chronically Exposed to Cocaine and Alcohol. Proceedings of the National Academy of Sciences, 108 (16), 6626–31. https://doi.org/10.1073/pnas.1018514108.
Van der Geer, J., Hanraads, J. A. J., & Lupton, R. A. (2000). The art of writing a scientific article. Journal of Science Communication, 163, 51–59.
Strunk, W., Jr., & White, E. B. (1979). The elements of style (3rd ed.). New York: MacMillan.
Mettam, G. R., & Adams, L. B. (1999). How to prepare an electronic version of your article. In B. S. Jones & R. Z. Smith (Eds.), Introduction to the electronic age (pp. 281–304). New York: E-Publishing Inc.
Fachinger, J., den Exter, M., Grambow, B., Holgerson, S., Landesmann, C., Titov, M., et al. (2004). Behavior of spent HTR fuel elements in aquatic phases of repository host rock formations, 2nd International Topical Meeting on High Temperature Reactor Technology.  Beijing, China, paper #B08.
Fachinger, J. (2006). Behavior of HTR fuel elements in aquatic phases of repository host rock formations. Nuclear Engineering & Design, 236, 54.
Journal of Epigenetics
Volume 1, Issue 1
Winter 2019
Pages 1-7

Files

History

  • Receive Date: 23 May 2018
  • Revise Date: 02 January 2019
  • Accept Date: 19 February 2019

Share

How to cite

Statistics