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Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia

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Abstract

The activity of complex I of the mitochondrial respiratory chain has been found to be decreased in patients with Parkinson’s disease (PD), but no mutations have been identified in genes encoding complex I subunits. Recent studies have suggested that polymorphisms in mitochondrial DNA (mtDNA)-encoded complex I genes (MTND) modify susceptibility to PD. We hypothesize that the risk of PD is conveyed by the total number of nonsynonymous substitutions in the MTND genes in various mtDNA lineages rather than by single mutations. To test this possibility, we determined the number of nonsynonymous substitutions of the seven MTND genes from 183 Finns. The differences in the total number of nonsynonymous substitutions and the nonsynonymous to synonymous substitution rate ratio (K a /K s ) of MTND genes between the European mtDNA haplogroup clusters (HV, JT, KU, IWX) were analysed by using a statistical approach. Patients with PD (n=238) underwent clinical examination together with mtDNA haplogroup analysis and the clinical features between patient groups defined by the number of nonsynonymous substitutions were compared. Our analysis revealed that the haplogroup clusters HV and KU had a lower average number of amino acid replacements and a lower K a /K s ratio in the MTND genes than clusters JT and IWX. Supercluster JTIWX with the highest number of amino acid replacements was more frequent among PD patients and even more frequent among patients with PD who developed dementia. Our results suggest that a relative excess of nonsynonymous mutations in MTND genes in supercluster JTWIX is associated with an increased risk of PD and the disease progression to dementia.

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Acknowledgements

The authors thank Ms. Irma Vuoti for her expert technical assistance. This study was supported by grants from the Medical Research Council of the Academy of Finland, the Sigrid Juselius Foundation and the Finnish Parkinson Association.

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Authors and Affiliations

  1. Department of Neurology, University Hospital and University of Kuopio, Kuopio, Finland

    Jaana Autere, Hilkka Soininen, Päivi Hartikainen & Merja Hallikainen

  2. Department of Neurology, Kanta-Häme Central Hospital, Hämeenlinna, Finland

    Jaana Autere

  3. Department of Neurology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland

    Jukka S. Moilanen, Saara Finnilä & Kari Majamaa

  4. Mediteknia, Clinical Research Center, Brain Research Unit, Kuopio, Finland

    Hilkka Soininen

  5. Department of Pathology, University of Kuopio, Kuopio, Finland

    Arto Mannermaa

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  1. Jaana Autere
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  2. Jukka S. Moilanen
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  3. Saara Finnilä
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Correspondence to Kari Majamaa.

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Autere, J., Moilanen, J.S., Finnilä, S. et al. Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia. Hum Genet 115, 29–35 (2004). https://doi.org/10.1007/s00439-004-1123-9

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  • DOI: https://doi.org/10.1007/s00439-004-1123-9

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