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

• Published in: International journal of molecular sciences Vol. 24; no. 2; p. 916
• Main Authors: López-Armas, Gabriela Del Carmen, Ramos-Márquez, Martha Eloisa, Navarro-Meza, Mónica, Macías-Islas, Miguel Ángel, Saldaña-Cruz, Ana Miriam, Zepeda-Moreno, Abraham, Siller-López, Fernando, Cruz-Ramos, José Alfonso
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04-01-2023; MDPI
• Subjects: Age; Aging; Biomarkers; Cell division; Chromosomes; Chronic illnesses; Copy number; Correlation; Disability; Disease; DNA Copy Number Variations; DNA, Mitochondrial - genetics; Humans; Inflammatory diseases; leukocyte telomere length; Leukocytes; Mitochondria; Mitochondrial DNA; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis, Relapsing-Remitting - genetics; Nervous system; Neurodegeneration; Neurological complications; Pathogenesis; Peripheral blood; Polymerase chain reaction; Regression analysis; relapsing-remittent multiple sclerosis; Senescence; Sensitivity; Statistical significance; Telomerase; Telomere - genetics; Telomeres; aging; leukocyte telomere length; disability; mitochondrial DNA; relapsing-remittent multiple sclerosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24020916

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 (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 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, p = 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.