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Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson’s disease risk in a Polish PD cohort

  • Parkinson's Disease and Allied Conditions - Original Article
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Abstract

mtDNA common variation is inconsistently reported to modify the risk of Parkinson’s disease (PD). We evaluated the impact of the mitochondrial haplogroups, subhaplogroups, coding and non-coding single-nucleotide polymorphisms on PD risk in 241 PD patients and 277 control subjects. After stratification by gender, we found that haplogroup J (OR 0.19; 95% CI 0.069–0.53; P = 0.0014) was associated with a lower PD risk in males. Unexpectedly, subhaplogroup analysis based on the control region (CR) polymorphisms demonstrated that subcluster K1a was more prevalent in healthy controls, while K1c was more frequent in PD patients (P = 0.025 and P = 0.011, respectively; two-tailed Fisher’s exact test). Additionally, we confirmed the hypothesis that sublineages (U4 + U5a1 + K+J1c + J2), previously proposed to partially uncouple oxidative phosphorylation (OXPHOS), decrease PD risk (P = 0.027, χ2 with Yates’ correction). The putative protective effect of uncoupling mtDNAs against PD might result from decreased production of reactive oxygen species. We propose that stratification into subhaplogroups or by gender could be necessary to reveal the involvement of specific mtDNA sublineages in PD pathogenesis.

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Acknowledgments

This work was supported by Ministry of Science (Poland) grants nr N N401 235134. We thank the individuals who participated in the study, Dr B. Tarnacka for the diagnosis of 7 PD cases and Dr. I. Soltyszewski for generous help.

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Authors and Affiliations

  1. Department of Neurodegenerative Disorders, Medical Research Center Polish Academy of Sciences, Pawińskiego 5, 02-106, Warsaw, Poland

    Katarzyna Gaweda-Walerych, Aleksandra Maruszak, Maria Styczynska, Maria Barcikowska & Cezary Zekanowski

  2. Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland

    Krzysztof Safranow

  3. Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland

    Monika Bialecka & Marek Drozdzik

  4. Department of Neurology, Ageing, Degenerative and Cerebrovascular Diseases, Medical University of Silesia, Katowice, Poland

    Gabriela Klodowska-Duda & Grzegorz Opala

  5. Department of Neurology, MSWiA Hospital, Warsaw, Poland

    Krzysztof Czyzewski

  6. Department of Neurology, St Adalbert Hospital and Department of Neurological-Psychiatric Nursing, Medical University, Gdańsk, Poland

    Jaroslaw Slawek

  7. Department of Neurology, Jagiellonian University Medical College, Kraków, Poland

    Monika Rudzinska

  8. Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA

    Jeffrey A. Canter

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  1. Katarzyna Gaweda-Walerych
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  9. Maria Styczynska
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  10. Grzegorz Opala
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  11. Marek Drozdzik
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  12. Jeffrey A. Canter
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  13. Maria Barcikowska
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  14. Cezary Zekanowski
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Corresponding author

Correspondence to Cezary Zekanowski.

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Gaweda-Walerych, K., Maruszak, A., Safranow, K. et al. Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson’s disease risk in a Polish PD cohort. J Neural Transm 115, 1521–1526 (2008). https://doi.org/10.1007/s00702-008-0121-9

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  • DOI: https://doi.org/10.1007/s00702-008-0121-9

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