title: Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease.
abstract: OBJECTIVE
  Dysfunction of mitochondrial DNA polymerase gamma (POLG) has been recently recognized as an important cause of inherited neurodegenerative diseases. We have reported dominant and recessive inheritance of parkinsonism, mitochondrial myopathy, and premature amenorrhea in five ethnically distinct families with POLG1 mutations. This prompted us to carry out a detailed analysis of the coding region and intron-exon boundaries of POLG1 in Finnish patients with idiopathic sporadic Parkinson disease (PD) and in nonparkinsonian controls.
  
  
  METHODS
  The coding region of POLG1 was analyzed in 140 Finnish patients with PD and their 127 spouses as age- and ethnically matched controls. Further, we analyzed the intragenic CAG-repeat region of POLG1 in 126 additional patients with nonparkinsonian neurologic disorders and in 516 Finnish population controls.
  
  
  RESULTS
  We found clustering of rare variants of the POLG1 CAG-repeat, encoding a polyglutamine tract, in Finnish patients with idiopathic PD as compared to their spouses (p = 0.003; OR 3.01, 95% CI 1.35 to 6.71), population controls (p = 0.001; OR 2.45, 95% CI 1.45 to 4.14), and patients with nonparkinsonian neurologic disorders (p = 0.05, OR 1.98, 95% CI 0.97 to 4.05). We found several amino acid substitutions, none of them associating with PD. These included a previously parkinsonism-associated POLG variant Y831C, found in one patient with PD, but also in five controls, suggesting that it is a neutral amino acid polymorphism.
  
  
  CONCLUSIONS
  Our results suggest that POLG polyglutamine tract variants should be considered as a predisposing genetic factor in idiopathic sporadic Parkinson disease.
authors.affiliation: Research Program of Molecular Neurology, Biomedicum-Helsinki, Helsinki University, Helsinki, Finland.
authors.forename: P T
authors.initials: PT
authors.lastname: Luoma
authors.forename: J
authors.initials: J
authors.lastname: Eerola
authors.forename: S
authors.initials: S
authors.lastname: Ahola
authors.forename: A H
authors.initials: AH
authors.lastname: Hakonen
authors.forename: O
authors.initials: O
authors.lastname: Hellström
authors.forename: K T
authors.initials: KT
authors.lastname: Kivistö
authors.forename: P J
authors.initials: PJ
authors.lastname: Tienari
authors.forename: A
authors.initials: A
authors.lastname: Suomalainen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D016366:Open Reading Frames / Q000235:genetics; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D010455:Peptides / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers; D010455:Peptides; C097188:polyglutamine; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human