| Summary: | <p>Abstract</p> <p>Background</p> <p>Mitochondrial dysfunction, oxidative damage and the accumulation of somatic mutations in mitochondrial DNA (mtDNA) have been associated with certain neurodegenerative disorders. Previous studies have also provided controversial results on the association of mtDNA haplogroups with susceptibility to Alzheimer's disease (AD), but possible relationships between mtDNA and frontotemporal lobar degeneration (FTLD) have been less frequently studied.</p> <p>Methods</p> <p>We analysed the role of mtDNA and its maintenance enzymes in 128 early-onset AD (eoAD) and in 66 FTLD cases. Patients and 99 controls were collected from a defined region of Finland, that of Northern Ostrobothnia, for the determination of mtDNA haplogroups and the analysis of two common mtDNA mutations (m.3243A>G, m.8344A>G). In addition, screening was performed for five common <it>POLG1 </it>mutations (T251I, A467T, P587L, W748S and Y955C) and all the coding exons of the <it>PEO1 </it>and <it>ANT1 </it>genes were screened for mutations.</p> <p>Results</p> <p>The frequency of haplogroup cluster IWX was 2.3 fold higher among the FTLD cases than in the controls (OR 2.69, 95% CI 1.09-6.65, <it>p </it>= 0.028). The frequency of mtDNA haplogroups or clusters did not differ between the eoAD cases and controls. The two mtDNA mutations and five <it>POLG1 </it>mutations were absent in the eoAD and FTLD patients. No pathogenic mutations were found in the <it>PEO1 </it>or <it>ANT1 </it>genes.</p> <p>Conclusions</p> <p>We conclude that the haplogroup cluster IWX was associated with FTLD in our cohort. Further studies in other ethnically distinct cohorts are needed to clarify the contribution of mtDNA haplogroups to FTLD and AD.</p>
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