Association of Mitochondrial DNA Genomic Variation with Risk of Pick’s disease

Objective: To determine if stable polymorphisms which define mitochondrial haplogroups in mitochondrial DNA (mtDNA) are associated with Pick’s disease risk, we genotyped 52 pathologically confirmed Pick’s disease cases and 910 neurologically healthy controls and performed case-control association analysis.

Methods: 52 pathologically confirmed Pick’s disease cases from Mayo Clinic Florida (N=38) and the University of Pennsylvania (N=14) and 910 neurologically healthy controls collected from Mayo Clinic Florida were genotyped for unique mtDNA haplogroup-defining variants. Mitochondrial haplogroups were determined, and in a case-control analysis, associations of mtDNA haplogroups with risk of Pick’s disease were evaluated using logistic regression models that were adjusted for age and sex.

Results: No individual mtDNA haplogroups or super-haplogroups were significantly associated with risk of Pick’s disease after adjusting for multiple testing (P<0.0021 considered significant). However, nominally significant (P<0.05) associations towards an increased risk of Pick’s disease were observed for mtDNA haplogroup W (5.8% cases versus 1.6% controls, OR=4.78, P=0.020) and sub-haplogroup H4 (5.8% cases versus. 1.2% controls, OR=4.82, P=0.021).

Conclusion: Our findings indicate that mtDNA variation is not a disease driver but may influence disease susceptibility. Ongoing genetic assessments in larger cohorts of PiD are currently underway.