SDHAP3 Epigenetic Alterations in Fetuses Exposed to Maternal Smoking and Other Neurodevelopmental Disorders

Samantha Fine

 Introduction: The gene Succinate Dehydrogenase Flavoprotein Subunit A (SDHAP3) has epigenetic alterations in fetuses exposed to maternal smoking and other neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia, and down syndrome (DS)1-4. Although maternal smoking during pregnancy and the above mentioned neurodevelopmental disorders have vastly different symptoms and underlying causes, all of these disorders affect brain development and more specifically, contain epigenetic alterations of the SDAHP3 gene. These neurodevelopmental disorders also have been implicated in mitochondrial dysfunction5-7. The SDHAP3 gene, although precise function is unknown, is currently thought to be related to mitochondrial function5. Epigenetic research has grown significantly over the past decade and now, epigenetic biomarkers are being used for diagnostics and disease treatment8. There is no literature that relates epigenetic alterations of SDHAP3 to all of its neurodevelopmental disorders. By better understanding SDHAP3 and its epigenetic role in neurodevelopmental disorders and fetal exposure to maternal smoking, perhaps the pathophysiology and treatment of these disorders can be better understood. Methods: Brain tissue from second-trimester human fetuses exposed and unexposed to maternal smoking were analyzed with the Illumina Infinium Human Methylation 450BeadChip microarrays to locate genes with altered DNA methylation sites1. Similarly, post-mortem brain tissue samples of individuals with and without ASD were analyzed with the same DNA methylation kit2. Post-mortem brain tissue samples from individuals with and without DS were also analyzed with the same DNA methylation kit3. Post-mortem brain tissue samples from individuals with and without schizophrenia were also analyzed with the same DNA methylation kit4. Results: SDHAP3 was found to be hypomethylated in fetuses exposed to smoking in comparison to fetuses unexposed to smoking1. SDHAP3 was hypermethylated in individuals with ASD in comparison to those without ASD2. SDHAP3 was hypermethylated in individuals with DS in comparison to those without DS and similarly, SDHAP3 was hypermethylated in individuals with schizophrenia in comparison to those without schizophrenia3,4. Conclusion: SDHAP3 gene is epigenetically altered in patients with schizophrenia, ASD, and DS, as well as fetuses exposed to maternal smoking. For any child with a neurodevelopmental disorder, early diagnosis and early intervention are key to improved outcomes9.  Because SDHAP3 was found to be a key gene to be epigenetically altered, this could be a potential biomarker or target for neurodevelopmental disorder therapy. Further investigation of SDHAP3 is needed, as it could clarify how epigenetic alterations of SDHAP3 contribute to the pathophysiology of schizophrenia, ASD, DS, and fetal exposure to smoking.

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