Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease

J.M. van der Walt; K.K. Nicodemus; E.R. Martin; W.K. Scott; M.A. Nance; R.L. Watts; J.P. Hubble; J.L. Haines; W.C. Koller; K. Lyons; R. Pahwa; M.B. Stern; A. Colcher; B.C. Hiner; J. Jankovic; W.G. Ondo; F.H. Allen Jr.; C.G. Goetz; G.W. Small; F. Mastaglia; J.M. Stajich; A.C. McLaurin; L.T. Middleton; B.L. Scott; D.E. Schmechel; M.A. Pericak-Vance; J.M. Vance

doi:10.1086/373937

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Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease

Journal article

Peer reviewed

Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease

J.M. van der Walt, K.K. Nicodemus, E.R. Martin, W.K. Scott, M.A. Nance, R.L. Watts, J.P. Hubble, J.L. Haines, W.C. Koller, K. Lyons, …

The American Journal of Human Genetics, Vol.72(4), pp.804-811

2003

DOI: https://doi.org/10.1086/373937

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Abstract

Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34–0.91; P=.02) or K (OR 0.52; 95% CI 0.30–0.90; P=.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39–0.73; P=.0001). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27–0.71; P=.0009). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22–0.93; P=.03). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.

Details

Title: Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease
Authors/Creators: J.M. van der Walt (Author/Creator) - Duke University
K.K. Nicodemus (Author/Creator) - Duke University
E.R. Martin (Author/Creator) - Duke University
W.K. Scott (Author/Creator) - Duke University
M.A. Nance (Author/Creator) - Struthers Parkinson Center, Golden Valley, MN;
R.L. Watts (Author/Creator) - Emory University
J.P. Hubble (Author/Creator) - The Ohio State University
J.L. Haines (Author/Creator) - Vanderbilt University Medical Center
W.C. Koller (Author/Creator) - University of Miami
K. Lyons (Author/Creator) - University of Miami
R. Pahwa (Author/Creator) - University of Kansas Medical Center
M.B. Stern (Author/Creator) - University of Pennsylvania Health System
A. Colcher (Author/Creator) - University of Pennsylvania Health System
B.C. Hiner (Author/Creator) - Marshfield Clinic
J. Jankovic (Author/Creator) - Baylor College of Medicine
W.G. Ondo (Author/Creator) - Baylor College of Medicine
F.H. Allen Jr. (Author/Creator)
C.G. Goetz (Author/Creator) - St. Luke's Hospital
G.W. Small (Author/Creator) - St. Luke's Hospital
F. Mastaglia (Author/Creator) - The University of Western Australia
J.M. Stajich (Author/Creator) - Duke University
A.C. McLaurin (Author/Creator) - Duke University
L.T. Middleton (Author/Creator) - (GlaxoSmithKline)
B.L. Scott (Author/Creator) - Struthers Parkinson Center, Golden Valley, MN;
D.E. Schmechel (Author/Creator) - Duke University
M.A. Pericak-Vance (Author/Creator) - Duke University
J.M. Vance (Author/Creator) - Duke University
Publication Details: The American Journal of Human Genetics, Vol.72(4), pp.804-811
Publisher: Elsevier Inc.
Identifiers: 991005545270407891
Copyright: © 2003 The American Society of Human Genetics.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.197 Molecular & Cell Biology - Mitochondria; 1.197.564 Mitochondrial Function
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics