Mitochondrial complex I gene variations; as a potential genetic risk factor in pathogenesis of multiple sclerosis

J Neurol Sci. 2014 Oct 15;345(1-2):220-3. doi: 10.1016/j.jns.2014.07.051. Epub 2014 Jul 28.


Background and purpose: Multiple sclerosis (MS) is an autoimmune-mediated inflammatory and debilitating disease of the central nervous system. Several investigations have suggested that the mitochondrial DNA encoded subunits of complex I gene variations are involved in the progression of MS. In this study, we investigated the possible association between mitochondrial complex I gene variations and MS in a Filipino population.

Material and methods: A total of 300 individuals were included in the present study, two-hundred patients with MS clinical symptoms, and one-hundred healthy subjects without MS clinical features. We amplified target genes of mtDNA using polymerase chain reaction technique (PCR), and sequenced these to evaluate mitochondrial complex I gene variations.

Results: We found nine variations (Nt 4216 T>C, Nt 5153 A>G, Nt 10142 C>T, Nt 11353 T>C, Nt 11935 T>C, Nt 12062 C>T, Nt 13042 G>A, Nt 13708 G>A and Nt 14179 G>A) in mtDNA-encoded complex I subunit genes. Our results showed that the prevalence of ND1, ND2, ND3, ND4 and ND5 gene variations was significantly higher in patients than in healthy controls (P<0.0001). Whereas, the frequency of Nt 14179 G>A variation in ND6 gene was significantly higher in the control group compared with the patients (P<0.0001).

Conclusion: Taken together our data supports a strongly positive association between mitochondrial complex I gene variations and MS pathogenesis in a Filipino population.

Keywords: Complex I genes; Mitochondrial DNA variations; Multiple sclerosis; mtDNA.

MeSH terms

  • Adult
  • Chi-Square Distribution
  • Electron Transport Complex I / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Multiple Sclerosis / genetics*
  • Philippines
  • Risk Factors


  • Electron Transport Complex I