Abstract
As a complex neurodevelopmental disorder, autism affects children in three major cognitive domains including social interactions, language learning and repetitive stereotyped behaviors. Abnormal regulation of cell proliferation in the brain during the embryonic period via the TGF-β signaling pathway and TRIM33 gene that encodes a protein with a corepressor and regulatory role in this pathway has been considered as an etiology for autism. Here, we investigated the association of a variation of TRIM33 with autism symptoms at levels of mRNA and protein expression. We used Autism Diagnostic Interview-Revised (ADI-R) and Childhood Autism Rating Scale (CARS) as behavioral diagnostic tools. Normal and autistic children were genotyped for a TRIM33 polymorphism (rs11102807), and then expression was assessed at transcriptional and translational levels. Results demonstrated that the frequency of the homozygous A allele (AA genotype of rs11102807) was significantly higher in children with autism (P < 0.001), whereas carriers of the G allele were mostly among healthy individuals. Children homozygous for the rs11102807 A allele were associated with an increase in CARS and ADI-R scores, indicating a significant correlation with autism symptoms. TRIM33 gene expression at both mRNA (P < 0.01) and protein (P < 0.001) levels was significantly higher in controls compared to autistic children. A remarkable association between higher TRIM33 gene expression at the transcriptional level and lower scores for both CARS and ADI-R was observed in non-autistic children. It seems that rs11102807 modulates the function and expression of the TRIM33 gene, implying that the A allele may increase the risk of autism in children by reducing gene expression and altering the TGF-β signaling pathway.
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Acknowledgements
We thank Dr. Reza Falak for his assistance in this study.
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This work was supported by the Iran University of Medical Sciences (IUMS) [grant number: 26988–87-04–94].
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Research conception and design: Sattar Norouzi Ofogh, Esmaeil Shahsavand Ananloo, Mohammad Taghi Joghataei, Homa Rasoolijazi. Data acquisition: Sattar Norouzi Ofogh, Fatemeh Alizadeh, Zahra Shahrivar. Data analysis and interpretation: Sattar Norouzi Ofogh, Bahman Sadeghi, Ali Bozorgmehr. Figure and schematics preparation: Sattar Norouzi Ofogh, Bahman Sadeghi, Ali Bozorgmehr. Manuscript preparation: Sattar Norouzi Ofogh, Bahman Sadeghi, Homa Rasoolijazi. All authors have read and approved the final article.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the APA, institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was conducted with informed consent of the participants, and was approved by the Ethics Committee of the Iran University of Medical Sciences, No. IR.IUMS.REC 1394.94–04-87–26988.
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Cases were recruited from Roozbeh Hospital at Tehran University of Medical Sciences (TUMS). Informed consent was obtained from all participants and their parents or legal guardians.
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Norouzi Ofogh, S., Rasoolijazi, H., Shahsavand Ananloo, E. et al. Alteration of TRIM33 Expression at Transcriptional and Translational Levels is Correlated with Autism Symptoms. J Mol Neurosci 71, 1368–1377 (2021). https://doi.org/10.1007/s12031-020-01783-6
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DOI: https://doi.org/10.1007/s12031-020-01783-6