RORA and Autism in The Isfahan Population: Is There An Epigenetic Relationship

(Pages: 540-546)

Mansoor Salehi, Ph.D, ¹Elahe Kamali, M.Sc, ²Mojgan Karahmadi, M.D, ^3,*Seyyed mohammad Mousavi, M.Sc, ^4,5,*

1-Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2-Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran

3-Behavioral Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

4-Genetic and Identification Lab, Legal Medicine Center, Isfahan, Iran

5-Cellular and Molecular Research Center, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

*Corresponding Addresses: P.O.Box: 81746-73461 Behavioral Sciences Research Center Isfahan University of Medical Sciences Isfahan Iran P.O.Box: 8165875735 Genetic and Identification Lab Legal Medicine Center Isfahan Iran Emails:karahmadi@med.mui.ac.ir,prk_seyyed@yahoo.com

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Salehi Mansoor, Kamali Elahe, Karahmadi Mojgan, Mousavi Seyyed mohammad. RORA and Autism in The Isfahan Population: Is There An Epigenetic Relationship. Cell J. 2017; 18(4): 540-546.

Abstract

Objective

Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptor- related orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region. This may thus explain a significant part of the molecular pathogenesis of autism. Therefore, we aimed to confirm this finding by implementing a case-control (experimental) study in the population of Isfahan.

Materials and Methods

The methylation status of a 136 bp sequence of a GpG island (encompassing 13 CpG sites) in the RORA promoter region (positions -200 to -64) as an experimental study was examined in the lymphocyte cells of 30 autistic children after sodium bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay compared with normal children. Also, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to evaluate MCA-Meth analysis results.

Results

This study revealed no methylation in the examined promoter regions in both autistic and normal children, with the melting curve of all studied samples being comparable to that of the non-methylated control. The results of MCA-Meth analysis were also consistent with qRT-PCR results. We therefore observed no significant difference in the levels of RORα transcripts in the blood lymphocytes between autistic and healthy children.

Conclusion

The methylation of the RORA promoter region may not be considered as a common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis of autism remains unclear in the population investigated.

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