Investigation of the correlation between mildly deleterious mtDNA Variations and the clinical progression of multiple sclerosis

Abstract

Background: Evidence suggests that mitochondrial DNA (mtDNA) variation at a population level may influence susceptibility to, or the clinical progression of Multiple Sclerosis (MS).

Objective: To determine if mtDNA population variation is linked to the clinical progress of MS.

Methods: Using the complete mtDNA sequences of 217 MS patients, we applied the new 'variant load' model, designed as a framework by which to examine the role of mtDNA variation in the context of complex clinical disease.

Results: No significant association was detected between mtDNA 'variant load'and the clinical measures of progression.

Conclusion: Our results suggest that mtDNA population variation does not play a substantial role in the clinical progression of MS; however, modest effects and/or effects in a subgroup of patients cannot be entirely excluded. Results do not exclude the possibility of detecting an association between variation and more strictly quantified variables obtained from histopathologically-stained specimens. The results further illustrate the method's applicabilityto other disease phenotypes.

Keywords: Haplogroup; Mitochondrial DNA (mtDNA); Multiple sclerosis, Disease progression; Variant load model (VLM).