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...
Main Authors: | , , , , , , , |
---|---|
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 |