Mitochondrial DNA variants in inclusion body myositis

Mitochondrial DNA variants have been shown to be associated with many disea ses, Mutations at mitochondrial DNA nucleotide positions 3192, 3196, 3397 a nd 4336 have been described in association with late-onset Alzheimer's dise ase. The pathological similarities between inclusion body myositis and Alzh eimer's disease prompted an analysis of the relationship between the report ed mutations and sporadic inclusion body myositis. The 4336G variant was no t significantly increased in patients with inclusion body myositis or Alzhe imer's disease when compared to controls. None of the patients with inclusi on body myositis carried mutations at nucleotide positions 3192, 3196 and 3 397. A transition at nucleotide position 4580 was detected in some patients with inclusion body myositis and Alzheimer's disease but was not significa ntly higher in frequency when compared to controls. Phylogenetic analysis s howed that the 4336G and 4580A variants clustered together in their respect ive group. A group of patients with inclusion body myositis also clustered together an a separate branch of the phylogenetic tree. Closer investigatio n of this group revealed a common polymorphism at nucleotide position 16311 . The frequency of the 16311C variant was higher in inclusion body myositis than in Alzheimer's disease and controls, although when only caucasian pat ients were considered the increased frequency was not statistically signifi cant. Further studies will be required to determine whether this variant pl ays a role in the pathogenesis of inclusion body myositis. (C) 2000 Elsevie r Science B.V. All rights reserved.