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bioRxiv · 10.1101/2020.07.17.209650

Is methylation of the CTLA-4 gene promoter region an epigenetic mechanism of autoimmune thyroiditis in hepatitis C? In silico experimental observation

Matos de Oliveira, G. C.·Teles Aragao, A. Z. F.·Oliveira Andrade, L. J. d.
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Abstract

IntroductionCytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a crucial immune control point receptor that regulates T cell activation. Epigenetic mechanisms, such as DNA methylation and histone modifications, modulate DNA packaging in the nucleus and influence Gene expression. Autoimmune thyroiditis may be associated with hepatitis C virus (HCV) infection as well as the CTLA-4 Gene. ObjectiveTo in silico simulate the methylation of the promoter region of CTLA-4 gene as an epigenetic factor triggering autoimmune thyroiditis by HCV. MethodsWe analyzed by in silico simulation the hypermethylation scenarios of the CTLA-4 Gene promoter region, aligning CTLA-4 and HCV sequences (genotypes 1, 2 and 3) through BLAST software - http://blast.ncbi.nlm.nih.gov/Blast.cgi, and identifying their methylated and unmethylated CpG sites. After the sequences obtained with the alignment of the methylation points by MultAlin program, the consensus sequences obtained were submitted to the BLAST similarity search. The GC content calculation and HCV annotation were performed using ENDMEMO (http://www.endmemo.com/bio/gc.php). The MethPrimer was used to identify and locate the methylation CpGi within the HCV genome. ResultsThe location of CTLA-4 on chromosome 2 and the alignment of the amino acid sequences are presented: CTLA-4 and HCV genotype 1, CTLA-4 and HCV genotype 2 and CTLA-4 and HCV genotype 3 are presented, as well as the methylation sites. ConclusionIn susceptible individuals, hypermethylation promotes reduced CTLA-4 expression and increases the risk of autoimmune thyroiditis in HCV-infected individuals.

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Matos de Oliveira, G. C., Teles Aragao, A. Z. F., Oliveira Andrade, L. J. d.. 2020-07-19. Is methylation of the CTLA-4 gene promoter region an epigenetic mechanism of autoimmune thyroiditis in hepatitis C? In silico experimental observation. https://doi.org/10.1101/2020.07.17.209650

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