title: Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease.
abstract: Mitochondrial dysfunction originating from mutations in Complex I genes may play a role in the pathogenesis of Parkinson's disease (PD). In this study, the entire ND1 coding sequence was sequenced in 84 newly diagnosed PD cases and 127 age/gender-matched controls. Numerous missense mutations were found at low frequency (<5%), whereas a thymidine to cytosine missense mutation at position 4216 that results in the replacement of tyrosine with histidine was found in 25% of the PD case samples and in 18% of the controls. When calculated according to gender, the 4216 mutation was observed in 26% of the male cases versus 16% of male controls (Odds Ratio [OR] = 1.85; 95% CI = 0.79-4.34). In contrast, females exhibited approximately equal frequencies among cases (22.5%) and controls (21%), yielding an OR of 1.08 (95% C.I. = 0.36-3.22). The findings indicate only a weak association of this genetic variant with PD.
authors.affiliation: Department of Environmental Health, University of Washington, Seattle 98195-7234, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Kirchner
authors.forename: S E
authors.initials: SE
authors.lastname: Hallagan
authors.forename: F M
authors.initials: FM
authors.lastname: Farin
authors.forename: J
authors.initials: J
authors.lastname: Dilley
authors.forename: P
authors.initials: P
authors.lastname: Costa-Mallen
authors.forename: T
authors.initials: T
authors.lastname: Smith-Weller
authors.forename: G M
authors.initials: GM
authors.lastname: Franklin
authors.forename: P D
authors.initials: PD
authors.lastname: Swanson
authors.forename: H
authors.initials: H
authors.lastname: Checkoway
mesh_terms: D006801:Humans; D019476:Insect Proteins / Q000032:analysis / Q000235:genetics*; D008214:Lymphocytes / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009245:NADH Dehydrogenase; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D019476:Insect Proteins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human