Molecular Biology Reports

, Volume 40, Issue 8, pp 5123–5128

Evaluation of polymorphism, hypermethylation and expression pattern of CTLA4 gene in a sample of Iranian patients with schizophrenia


    • Department of BiologyUniversity of Sistan and Baluchestan
  • Shahram Vaziri
    • Department of PsychologyIslamic Azad University, Roodehen Branch
  • Nahid Dahmardeh
    • Department of BiologyUniversity of Sistan and Baluchestan
  • Adam Torkamanzehi
    • Department of BiologyUniversity of Sistan and Baluchestan

DOI: 10.1007/s11033-013-2614-3

Cite this article as:
Kordi-Tamandani, D.M., Vaziri, S., Dahmardeh, N. et al. Mol Biol Rep (2013) 40: 5123. doi:10.1007/s11033-013-2614-3


The cytotoxic T lymphocyte-associated antigen 4 gene (CTLA4) has a crucial role in regulation of T cell proliferation and mediates T cell apoptosis by encoding the T cell receptor. Schizophrenia (SCZ) patients often have abnormalities in terms of the function and development of the immune system. The aim of the present study was to investigate promoter variation and expression profile of the CTLA4 gene in patients with SCZ. We isolated genomic DNA from peripheral blood of 94 individuals with SCZ and 99 healthy control subjects. Genotypic analysis of CTLA4 (−318) was done by Tetra-ARMS-PCR. Methylation-specific polymerase chain reaction (MS-PCR) was used to estimate promoter hypermethylation of the CTLA4 gene. In addition, we investigated CTLA4 mRNA levels in 34 blood samples from cases and healthy controls using real-time reverse transcription PCR. The CT genotype of CTLA4 has a significantly protective effect on the risk to SCZ (OR = 0.44; 95 % CI 0.18–1.06, P = 0.007) in comparison with the wild CC genotype. Promoter methylation of the CTLA4 gene increased the risk of disease statistically (OR = 3.82, 95 % CI 1.34–10.9, P = 0.015) in cases when compared to healthy controls in blood samples. The mRNA expression level results showed statistically significant differences (P < 0.0001) between cases (n = 17) and healthy controls (n = 17). To the best of our knowledge, this is the first evidence showing that promoter methylation of the CTLA4 gene along with transition of C to T was linked to a significantly higher expression of CTLA4 mRNA levels in patients with SCZ.



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© Springer Science+Business Media Dordrecht 2013