Ghada Al-Kafaji, Maram A Alharbi, Noureddine Ben Khalaf, Safia Abdulsalam Messaoudi, Safa Taha, Abdulqader Daif, Halla F Bakheit, Laila D. Rizk, Ahmad A Farahat, Mohamed Jailani, Bashayer H. Ebrahim and Moiz Bakhiet
The impaired mitochondrial function has been implicated in the pathogenicity of multiple sclerosis (MS), a chronic inflammatory, demyelinating, and neurodegenerative disease of the CNS. We investigated whether variants in the genes encoding mitochondrial NADH dehydrogenase (ND1-ND6 and ND4L) of complex I are involved in MS. We also investigated if mitochondrial DNA copy number (mtDNA-CN) alteration in the peripheral blood is implicated in the pathogenicity of MS and could serve as a disease biomarker. The study included 124 Saudi subjects, 60 patients with relapsing-remitting MS (RRMS) and 64 healthy individuals. Genomic DNA was extracted from peripheral blood. The mtDNA-encoded ND genes were amplified and sequenced, and the mtDNA-CN was quantified by real time PCR. Sequence analysis revealed several synonymous variants in ND genes in both patients and controls. However, four variants in the ND4 gene were identified as missense mutations in MS patients with either direct or indirect impact on complex I function. Analysis of mtDNA-CN showed that the mtDNA-CN was lower in patients than in controls. Subgroup analysis with stratification of patients based on disease duration (under or over 10 years) revealed that the mtDNA-CN was lower in the group with longer disease duration. The ROC curve analysis indicated a significant ability of mtDNA-CN to differentiate patients from controls.