Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Telomere Shortening linked to Disability and Mitochondrial DNA Copy Number in Patients with Relapsing-Remitting Multiple Sclerosis

Version 1 : Received: 1 December 2021 / Approved: 2 December 2021 / Online: 2 December 2021 (10:08:35 CET)
Version 2 : Received: 6 December 2021 / Approved: 7 December 2021 / Online: 7 December 2021 (12:35:12 CET)

How to cite: Cruz-Ramos, J.A.; López-Armas, G.D.C.; Díaz-Barba, E.I.; Navarro-Meza, M.; Macías-Islas, M.Á.; Saldaña-Cruz, A.M.; Zepeda-Moreno, A.; Pérez-Gómez, H.R.; Martínez-Hernández, A.; Ramos-Márquez, M.E. Telomere Shortening linked to Disability and Mitochondrial DNA Copy Number in Patients with Relapsing-Remitting Multiple Sclerosis. Preprints 2021, 2021120026. https://doi.org/10.20944/preprints202112.0026.v1 Cruz-Ramos, J.A.; López-Armas, G.D.C.; Díaz-Barba, E.I.; Navarro-Meza, M.; Macías-Islas, M.Á.; Saldaña-Cruz, A.M.; Zepeda-Moreno, A.; Pérez-Gómez, H.R.; Martínez-Hernández, A.; Ramos-Márquez, M.E. Telomere Shortening linked to Disability and Mitochondrial DNA Copy Number in Patients with Relapsing-Remitting Multiple Sclerosis. Preprints 2021, 2021120026. https://doi.org/10.20944/preprints202112.0026.v1

Abstract

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 disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p<00001; 75.14 ± 1.77 vs 68.06 ± 1.608, p<0.00001, respectively). The LTL and mtDNA-CN showed a linear correlation in RRMS with mild-moderate disability (r=0.2986, p=0.0351). In addition, in a binary logistic regression model the LTL can predict severe disability (AUC=0.697, p=0.0031, cutoff ≤ 3.0875 Kb, sensitivity= 73.1%, specificity=62.5%), the prediction is improved by including age to the model (AUC=0.765, <0.0001, sensitivity=78.26%, specificity=81.25%). Aging is closely linked to the development of disability in RRMS and can be evaluated through LTL and mtDNA-CN absolute quantification.

Keywords

Leukocyte telomere length; Mitochondrial DNA; Relapsing- Remittent Multiple Sclerosis; Disability; Aging

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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