Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the L...

Full description

Bibliographic Details
Main Authors: Gabriela del Carmen López-Armas, Martha Eloisa Ramos-Márquez, Mónica Navarro-Meza, Miguel Ángel Macías-Islas, Ana Miriam Saldaña-Cruz, Abraham Zepeda-Moreno, Fernando Siller-López, José Alfonso Cruz-Ramos
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/2/916
_version_ 1797441674890182656
author Gabriela del Carmen López-Armas
Martha Eloisa Ramos-Márquez
Mónica Navarro-Meza
Miguel Ángel Macías-Islas
Ana Miriam Saldaña-Cruz
Abraham Zepeda-Moreno
Fernando Siller-López
José Alfonso Cruz-Ramos
author_facet Gabriela del Carmen López-Armas
Martha Eloisa Ramos-Márquez
Mónica Navarro-Meza
Miguel Ángel Macías-Islas
Ana Miriam Saldaña-Cruz
Abraham Zepeda-Moreno
Fernando Siller-López
José Alfonso Cruz-Ramos
author_sort Gabriela del Carmen López-Armas
collection DOAJ
description Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (<i>p</i> = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, <i>p</i> = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, <i>p</i> = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, <i>p</i> = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.
first_indexed 2024-03-09T12:27:34Z
format Article
id doaj.art-3d061c188b584d35aaf62955a075214a
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T12:27:34Z
publishDate 2023-01-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-3d061c188b584d35aaf62955a075214a2023-11-30T22:32:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124291610.3390/ijms24020916Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy NumberGabriela del Carmen López-Armas0Martha Eloisa Ramos-Márquez1Mónica Navarro-Meza2Miguel Ángel Macías-Islas3Ana Miriam Saldaña-Cruz4Abraham Zepeda-Moreno5Fernando Siller-López6José Alfonso Cruz-Ramos7Laboratorio de Biomédica-Mecatrónica, Subdirección de Investigación y Extensión, Centro de Enseñanza Técnica Industrial Plantel Colomos, Guadalajara 44638, MexicoDepartamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoLaboratorio C. de Neuronutrición y Memoria, Departamento de Promoción, Preservación y Desarrollo de la Salud, Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán 49000, MexicoDepartamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDepartamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoDepartamento de Clínicas de la Reproducción Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoPrograma de Bacteriología, Facultad de Ciencias de la Salud, Universidad Católica de Manizales, Manizales 170002, ColombiaDepartamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, MexicoMultiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (<i>p</i> = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, <i>p</i> = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, <i>p</i> = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, <i>p</i> = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.https://www.mdpi.com/1422-0067/24/2/916leukocyte telomere lengthmitochondrial DNArelapsing-remittent multiple sclerosisdisabilityaging
spellingShingle Gabriela del Carmen López-Armas
Martha Eloisa Ramos-Márquez
Mónica Navarro-Meza
Miguel Ángel Macías-Islas
Ana Miriam Saldaña-Cruz
Abraham Zepeda-Moreno
Fernando Siller-López
José Alfonso Cruz-Ramos
Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
International Journal of Molecular Sciences
leukocyte telomere length
mitochondrial DNA
relapsing-remittent multiple sclerosis
disability
aging
title Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
title_full Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
title_fullStr Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
title_full_unstemmed Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
title_short Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
title_sort leukocyte telomere length predicts severe disability in relapsing remitting multiple sclerosis and correlates with mitochondrial dna copy number
topic leukocyte telomere length
mitochondrial DNA
relapsing-remittent multiple sclerosis
disability
aging
url https://www.mdpi.com/1422-0067/24/2/916
work_keys_str_mv AT gabrieladelcarmenlopezarmas leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT marthaeloisaramosmarquez leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT monicanavarromeza leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT miguelangelmaciasislas leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT anamiriamsaldanacruz leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT abrahamzepedamoreno leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT fernandosillerlopez leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber
AT josealfonsocruzramos leukocytetelomerelengthpredictsseveredisabilityinrelapsingremittingmultiplesclerosisandcorrelateswithmitochondrialdnacopynumber