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Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms

Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic polymorphisms of tandem-repeated noncoding DNA. These polymorphisms may serve as predictive biomarkers of various forms of epilepsy. ACAP3 is t...

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Autores principales: Suchkova, Irina O., Borisova, Elena V., Patkin, Eugene L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730309/
https://www.ncbi.nlm.nih.gov/pubmed/33276684
http://dx.doi.org/10.3390/ijms21239206
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author Suchkova, Irina O.
Borisova, Elena V.
Patkin, Eugene L.
author_facet Suchkova, Irina O.
Borisova, Elena V.
Patkin, Eugene L.
author_sort Suchkova, Irina O.
collection PubMed
description Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic polymorphisms of tandem-repeated noncoding DNA. These polymorphisms may serve as predictive biomarkers of various forms of epilepsy. ACAP3 is the protein regulating morphogenesis of neurons and neuronal migration and is an integral component of important signaling pathways. This study aimed to carry out an association analysis of the length polymorphism and DNA methylation of the UPS29 minisatellite of the ACAP3 gene in patients with epilepsy. We revealed an association of short UPS29 alleles with increased risk of development of symptomatic and cryptogenic epilepsy in women, and also with cerebrovascular pathologies, structural changes in the brain, neurological status, and the clinical pattern of seizures in both women and men. The increase of frequency of hypomethylated UPS29 alleles in men with symptomatic epilepsy, and in women with both symptomatic and cryptogenic epilepsy was observed. For patients with hypomethylated UPS29 alleles, we also observed structural changes in the brain, neurological status, and the clinical pattern of seizures. These associations had sex-specific nature similar to a genetic association. In contrast with length polymorphism epigenetic changes affected predominantly the long UPS29 allele. We suppose that genetic and epigenetic alterations UPS29 can modify ACAP3 expression and thereby affect the development and clinical course of epilepsy.
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spelling pubmed-77303092020-12-12 Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms Suchkova, Irina O. Borisova, Elena V. Patkin, Eugene L. Int J Mol Sci Article Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic polymorphisms of tandem-repeated noncoding DNA. These polymorphisms may serve as predictive biomarkers of various forms of epilepsy. ACAP3 is the protein regulating morphogenesis of neurons and neuronal migration and is an integral component of important signaling pathways. This study aimed to carry out an association analysis of the length polymorphism and DNA methylation of the UPS29 minisatellite of the ACAP3 gene in patients with epilepsy. We revealed an association of short UPS29 alleles with increased risk of development of symptomatic and cryptogenic epilepsy in women, and also with cerebrovascular pathologies, structural changes in the brain, neurological status, and the clinical pattern of seizures in both women and men. The increase of frequency of hypomethylated UPS29 alleles in men with symptomatic epilepsy, and in women with both symptomatic and cryptogenic epilepsy was observed. For patients with hypomethylated UPS29 alleles, we also observed structural changes in the brain, neurological status, and the clinical pattern of seizures. These associations had sex-specific nature similar to a genetic association. In contrast with length polymorphism epigenetic changes affected predominantly the long UPS29 allele. We suppose that genetic and epigenetic alterations UPS29 can modify ACAP3 expression and thereby affect the development and clinical course of epilepsy. MDPI 2020-12-02 /pmc/articles/PMC7730309/ /pubmed/33276684 http://dx.doi.org/10.3390/ijms21239206 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Suchkova, Irina O.
Borisova, Elena V.
Patkin, Eugene L.
Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms
title Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms
title_full Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms
title_fullStr Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms
title_full_unstemmed Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms
title_short Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms
title_sort length polymorphism and methylation status of ups29 minisatellite of the acap3 gene as molecular biomarker of epilepsy. sex differences in seizure types and symptoms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730309/
https://www.ncbi.nlm.nih.gov/pubmed/33276684
http://dx.doi.org/10.3390/ijms21239206
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