Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease.
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.
Kirchner
S C
SC
Department of Environmental Health, University of Washington, Seattle 98195-7234, USA.
Hallagan
S E
SE
Farin
F M
FM
Dilley
J
J
Costa-Mallen
P
P
Smith-Weller
T
T
Franklin
G M
GM
Swanson
P D
PD
Checkoway
H
H
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
D019476:Insect Proteins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human