RGD Reference Report - Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. - Rat Genome Database

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Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.

Authors: Van der Walt, JM  Nicodemus, KK  Martin, ER  Scott, WK  Nance, MA  Watts, RL  Hubble, JP  Haines, JL  Koller, WC  Lyons, K  Pahwa, R  Stern, MB  Colcher, A  Hiner, BC  Jankovic, J  Ondo, WG  Allen FH, JR  Goetz, CG  Small, GW  Mastaglia, F  Stajich, JM  McLaurin, AC  Middleton, LT  Scott, BL  Schmechel, DE  Pericak-Vance, MA  Vance, JM 
Citation: van der Walt JM, etal., Am J Hum Genet. 2003 Apr;72(4):804-11. Epub 2003 Feb 28.
RGD ID: 5490292
Pubmed: PMID:12618962   (View Abstract at PubMed)
PMCID: PMC1180345   (View Article at PubMed Central)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease susceptibilityIAGP 5490292DNA:SNP:cds:m.9055A>G (human)RGD 
Parkinson's disease susceptibilityISOMT-ATP6 (Homo sapiens)5490292; 5490292DNA:SNP:cds:m.9055A>G (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinsonism susceptibilityIAGP 5490292DNA:SNP:cds:m.9055A>GRGD 
Objects Annotated

Genes (Rattus norvegicus)
Mt-atp6  (mitochondrially encoded ATP synthase membrane subunit 6)

Genes (Mus musculus)
mt-Atp6  (ATP synthase 6, mitochondrial)

Genes (Homo sapiens)
MT-ATP6  (mitochondrially encoded ATP synthase membrane subunit 6)


Additional Information