Pharmacogenomics and Personalized Medicine (Feb 2022)

DNA Methylation Level of Transcription Factor Binding Site in the Promoter Region of Acyl-CoA Synthetase Family Member 3 (ACSF3) in Saudi Autistic Children

  • Algothmi K,
  • Alqurashi A,
  • Alrofaidi A,
  • Alharbi M,
  • Farsi R,
  • Alburae N,
  • Ganash M,
  • Azhari S,
  • Basingab F,
  • Almuhammadi A,
  • Alqosaibi A,
  • Alkhatabi H,
  • Elaimi A,
  • Jan M,
  • Aldhalaan H,
  • Alrafiah A,
  • Alhazmi S

Journal volume & issue
Vol. Volume 15
pp. 131 – 142

Abstract

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Khloud Algothmi,1 Amal Alqurashi,1 Aisha Alrofaidi,1 Mona Alharbi,1 Reem Farsi,1 Najla Alburae,1 Magdah Ganash,1 Sheren Azhari,1 Fatemah Basingab,1 Asma Almuhammadi,1 Amany Alqosaibi,2 Heba Alkhatabi,3,4 Aisha Elaimi,3,4 Mohammed Jan,5 Hesham Aldhalaan,6 Aziza Alrafiah,4 Safiah Alhazmi1 1Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3King Abdulaziz University, Centre of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia; 4Medical LaboratorySciencesDepartment,Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia; 5College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Center for Autism Research at King Faisal Specialist Hospital & Research Center (KFSH & RC), Riyadh, Saudi ArabiaCorrespondence: Aziza Alrafiah, P.O Box 80200, Jeddah, 21589, Saudi Arabia, Tel +966 126401000 Ext. 23495, Fax +966 126401000 Ext. 21686, Email [email protected]: DNA methylation (DNAm) is one of the main epigenetic mechanisms that affects gene expression without changing the underlying DNA sequence. Aberrant DNAm has an implication in different human diseases such as cancer, schizophrenia, and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that affects behavior, learning, and communication skills. Acyl-CoA synthetase family member 3 (ACSF3) encodes malonyl-CoA synthetase that is involved in the synthesis and oxidation of fatty acids. The dysregulation in such gene has been reported in combined malonic and methylmalonic aciduria associated with neurological symptoms such as memory problems, psychiatric diseases, and/or cognitive decline. This research aims to study DNAm in the transcription factor (TF) binding site of ACSF3 in Saudi autistic children. To determine whether the DNAm of the TF-binding site is a cause or a consequence of transcription regulation of ACSF3.Methods: RT-qPCR and DNA methylight qPCR were used to determine the expression and DNAm level in the promoter region of ACSF3, respectively. DNA and RNA were extracted from 19 cases of ASD children and 18 control samples from their healthy siblings.Results: The results showed a significant correlation between the gene expression of ACSF3 and specificity protein 1 (SP1) in 17 samples of ASD patients, where both genes were upregulated in 9 samples and downregulated in 8 samples.Conclusion: Although this study found no DNAm in the binding site of SP1 within the ACSF3 promoter, the indicated correlation highlights a possible role of ACSF3 and SP1 in ASD patients.Keywords: autism, DNA methylation, SP1, ACSF3, Saudi autistic children, DNAm

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