Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease

David K. Simon, Nathan Pankratz, Diane K. Kissell, Michael W. Pauciulo, Cheryl A. Halter, Alice Rudolph, Ronald F. Pfeiffer, William C. Nichols, Tatiana Foroud

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23 Scopus citations


Background: Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD.Methods: We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset.Results: The frequency of affected mothers of the proband with PD (83/167, 49.4%) was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4%) (Odds Ratio 1.22; 95%CI 0.83 - 1.81). After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother.Conclusions: These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic mDNA mutations, contribute to the risk of familial PD.

Original languageEnglish (US)
Article number53
JournalBMC medical genetics
Issue number1
StatePublished - Apr 1 2010

Bibliographical note

Funding Information:
The PROGENI study is supported by a grant from the NINDS: R01 NS37167 (TF). DKS is supported by a grant from the NINDS: 1R01NS058988. The GWAS genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. The authors have no financial conflicts of interest to disclose. PSG-PROGENI Steering Committee. University of Tennessee Health Science Center: R. F. Pfeiffer; University of Rochester: F. Marshall, D. Oakes, B. Ravina, A. Rudolph; Columbia University Medical Center: K. Marder; Indiana University School of Medicine: P.M. Conneally, T. Foroud, C. Halter; University of Kansas Medical Center: K. Lyons; Eli Lilly & Company: E. Siemers; Medical College of Ohio: L. Elmers; University of California, Irvine: N. Hermanowicz. PSG-PROGENI Investigators and Coordinators: Albany Medical College: S Factor, D Higgins, E Molho, S Evans; Banner Good Samaritan Medical Center: P Mahant, E Karoll; Barrow Neurological Institute: A Lieberman, H Shill, M Stacy, J Danielson, L Marlor, K Williamson; Baylor College of Medicine: J Jankovic, C Hunter; Beth Israel Deaconess Medical Center: D Simon, P Rose, P Ryan, L Scollins; Beth Israel Medical Center: R Saunders-Pullman, K Boyar, C Costan-Toth, E Ohmann; Brigham & Women’s Hospital: L Sudarsky, C Corwin; Brown University (Memorial Hospital of RI): J Friedman, K Chou, H Fernandez, M Lannon; CHUM - Hospital Notre-Dame: S Chouinard, M Panisset, J Hall, H Poiffaut; Cleveland Clinic Florida-Weston: N Galvez-Jimenez, A Podichetty, K Thompson, O Yastrubetskaya, M Braun; Clinical Neuroscience Center: P Lewitt, M Deangelis; Colorado Neurological Institute: C O’Brien, L Seeberger, R Kumar, C Dingmann, D Judd, D Miracle; Columbia University Medical Center: K Marder, J Fraser, J Harris; Creighton University: J Bertoni, C Peterson; Henry Ford Hospital: P Lewitt, P Kaminski, M Mcnamee; Hunter Homes Mcguire Veterans Medical Center: V Calabrese, P Roberge; Indiana University School of Medicine: J Wojcieszek, J Belden; Institute For Neurodegenerative Disorders: D Jennings, K Marek, S Mendick, P Becker; Johns Hopkins University: L Marsh, S Reich, B Dunlop, M Gerstenhaber, P Lowrimone; London Health Sciences Centre: M Jog, C Horn; LSU Health Sciences Center: R Zweig, C Hilliard; Mayo Clinic Jacksonville: R Uitti, M Turk; Mcfarland Neurosciences: T Ajax, J Mannetter; Medical College of Georgia: K Sethi, J Carpenter, B Dill, L Hatch, K Ligon, S Narayan; Medical College of Wisconsin: K Blindauer, K Abou-Samra, J Petit; Medical University of Ohio: L Elmer, E Aiken, K Davis, C Schell, S Wilson; Mount Sinai School of Medicine New York: M Velickovic, W Koller (Deceased), S Phipps; North Shore-LIJ Health System: A Feigin, M Gordon J Hamann, E Licari, M Marotta-Kollarus, B Shannon, R Winnick; Northshore University Healthsystem Glenbrook: M Rezak, G Medalle; Northwestern University: T Simuni, A Videnovic, A Kaczmarek, K Williams, M Wolff; NYU-New York University: A DiRoccoJ Lane, S Varanese; Ochsner Clinic Foundation: J Rao, M Cook; Ohio State University: M Fernandez, S Kostyk, J Hubble, A Campbell, C Reider, A Seward, G Shifroni; Oregon Health & Science University: R Camicioli, J Carter, J Nutt, P Andrews, S Morehouse, C Stone; Ottawa Hospital Civic Site: D Grimes, T Mendis, C Alcorn-Costa, J Conway, P Gray, K Haas; Pacific Health Research Institute: G Ross, S Terashita; Pacific Neuroscience Medical Group: J Sutton, B Hutchinson, J Young; Parkinson’s Disease & Movement Disorder Center: S Isaacson, R Delaney; Port City Neurology, Inc: E Drasby, M Lannon; Saskatoon District Health Board Royal University Hospital: A Rajput, A Rajput, L Klassen, T Shirley; Scott & White Hospital/Texas A&M University: B Manyam, P Simpson, J Whetteckey, B Wulbrecht; Southern Illinois University: R Elble, D Kelley; The Parkinson’s & Movement Disorder Institute: D Truong, K Frei, M Pathak, N Luong, T Tra, A Tran, J Vo; Toronto Western Hospital, University Health Network: A Lang, G Kleiner-Fisman, A Nieves, L Johnston, J So; UMDNJ-School of Osteopathic Medicine: G Podskalny, L Giffin; University of Buffalo: T Guttuso; University of Alabama at Birmingham: P Atchison, C Allen; University of Alberta: W Martin, M Wieler; University of Calgary: O Suchowersky, M Klimek; University of California Irvine: N Hermanowicz, S Niswonger, D Gonzalez; University of California San Diego: C Shults (Deceased), D Fontaine; University of California San Francisco: M Aminoff, C Christine, M Diminno, J Hevezi; University of Chicago: A Dalvi, U Kang, J Richman,, S Uy, J Young; University of Cincinnati: A Dalvi, A Sahay, M Gartner, D Schwieterman; University of Colorado Health Sciences Center: D Hall, M Leehey, S Culver, T Derian, K Howard; University of Connecticut: T Demarcaida, S Thurlow; University of Iowa: R Rodnitzky, J Dobson; University of Kansas Medical Center: K Lyons, R Pahwa, T Gales, S Thomas; University of Maryland School of Medicine: L Shulman, S Reich, W Weiner, M Cines, K Dustin, N Zappala; University of Miami: K Lyons, C Singer, W Koller (Deceased), W Weiner, L Zelaya; University of Minnesota: P Tuite, V Hagen, S Rolandelli, R Schacherer, J Kosowicz; University of New Mexico: P Gordon, J Werner; University of Puerto Rico School of Medicine: C Serrano, S Roque; University of Rochester: R Kurlan, D Berry, I Gardiner; University of South Florida: R Hauser, J Sanchez-Ramos, T Zesiewicz, S Carter, H Delgado, K Price, P Rodriguez; University of Tennessee Health Science Center: R Pfeiffer, L Davis, B Pfeiffer; University of Texas Southwestern Medical Center: R Dewey, B Hayward, G Huet, A Johnson, M Meacham, B Estes; Wake


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