Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

Feliciano, Luciana Maria; Sávio, André Luiz Ventura; de Castro Marcondes, João Paulo; da Silva, Glenda Nicioli; Salvadori, Daisy Maria Fávero

doi:10.1007/s12031-019-01408-7

Published: 04 November 2019

Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

Luciana Maria Feliciano¹,
André Luiz Ventura Sávio²,
João Paulo de Castro Marcondes³,
Glenda Nicioli da Silva⁴ &
Daisy Maria Fávero Salvadori ORCID: orcid.org/0000-0001-9323-3134¹

Journal of Molecular Neuroscience volume 70, pages 120–130 (2020)Cite this article

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Abstract

The etiology of multiple sclerosis (MS) is still not known, but the interaction of genetic, immunological, and environmental factors seem to be involved. This study aimed to investigate genetic alterations and the vitamin D status in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS). A total of 53 patients (29 RRMS; 24 SPMS) and 25 healthy subjects were recruited to evaluate the micronucleated cell (MNC) frequency and nuclear abnormalities in the buccal mucosa, gene expression profiling in mononuclear cells, and plasmatic vitamin D concentration in the blood. Results showed a higher frequency of cells with karyorrhexis (SPMS) and lower frequencies of nuclear pyknosis (RRMS and SPMS) and karyolysis (SPMS) in patients with MS. Significant increase in the frequency of MNC was detected in the buccal mucosa of RRMS and SPMS patients. HIF1A, IL13, IL18, MYC, and TNF were differentially expressed in MS patients, and APP was overexpressed in cells of RRMS compared to SPMS patients. No relationship was observed between vitamin D level and the differentially expressed genes. In conclusion, the cytogenetic alterations in the buccal mucosa can be important indicators of genetic instability and degenerative processes in patients with MS. Furthermore, our data introduced novel biomarkers associated with the molecular pathogenesis of MS.

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Acknowledgments

The authors are grateful to Brenda Anfilo for technical assistance and to Dr. Fábio H. Fernandes for the scientific illustration.

Funding

This study was supported by the National Council for Scientific and Technological Development (CNPq-471312/2012-6)—Brazil.

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Affiliations

Faculty of Medicine, UNESP–São Paulo State University, Botucatu, SP, Brazil
Luciana Maria Feliciano & Daisy Maria Fávero Salvadori
Health Science Dept., UNINOVE–Nove de Julho University, Bauru, SP, Brazil
André Luiz Ventura Sávio
CESMAC–University Center, Maceió, AL, Brazil
João Paulo de Castro Marcondes
Faculty of Pharmacy, UFOP–Federal University of Ouro Preto, Ouro Preto, MG, Brazil
Glenda Nicioli da Silva

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Luciana Maria Feliciano
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André Luiz Ventura Sávio
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João Paulo de Castro Marcondes
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Glenda Nicioli da Silva
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Daisy Maria Fávero Salvadori
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Correspondence to Daisy Maria Fávero Salvadori.

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Feliciano, L.M., Sávio, A.L.V., de Castro Marcondes, J.P. et al. Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis. J Mol Neurosci 70, 120–130 (2020). https://doi.org/10.1007/s12031-019-01408-7

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Received: 26 June 2019
Accepted: 26 September 2019
Published: 04 November 2019
Issue Date: January 2020
DOI: https://doi.org/10.1007/s12031-019-01408-7

Keywords

Multiple sclerosis
Vitamin D
Biomarkers
Buccal mucosa
Micronucleated cell