Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number.
Gabriela Del Carmen López-ArmasMartha Eloisa Ramos-MárquezMónica Navarro-MezaMiguel Angel Macías-IslasAna Miriam Saldaña-CruzAbraham Zepeda-MorenoFernando Siller-LópezJosé Alfonso Cruz-RamosPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- multiple sclerosis
- mitochondrial dna
- copy number
- white matter
- genome wide
- peripheral blood
- dna methylation
- early onset
- lymph node metastasis
- end stage renal disease
- systemic lupus erythematosus
- chronic kidney disease
- high intensity
- newly diagnosed
- ejection fraction
- rheumatoid arthritis
- prognostic factors
- brain injury
- patient reported outcomes