title: A rare truncating mutation in ADH1C (G78Stop) shows significant association with Parkinson disease in a large international sample.
abstract: BACKGROUND
  Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample.
  
  
  METHODS
  The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls.
  
  
  RESULTS
  The previously identified association with an ADH class IV allele remained significant (P<.02) in the extended Swedish study. Furthermore, in the international collaboration, the G78stop mutation in ADH1C was found in 22 (2.0%) of the PD patients but only in 6 controls (0.6%). This association was statistically significant (chi(2)(1) = 7.5; 2-sided P = .007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder.
  
  
  CONCLUSIONS
  Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. buervens@intra.nimh.nih.gov
authors.forename: Silvia
authors.initials: S
authors.lastname: Buervenich
authors.forename: Andrea
authors.initials: A
authors.lastname: Carmine
authors.forename: Dagmar
authors.initials: D
authors.lastname: Galter
authors.forename: Haydeh N
authors.initials: HN
authors.lastname: Shahabi
authors.forename: Bo
authors.initials: B
authors.lastname: Johnels
authors.forename: Björn
authors.initials: B
authors.lastname: Holmberg
authors.forename: Jarl
authors.initials: J
authors.lastname: Ahlberg
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.forename: Johanna
authors.initials: J
authors.lastname: Eerola
authors.forename: Olli
authors.initials: O
authors.lastname: Hellström
authors.forename: Pentti J
authors.initials: PJ
authors.lastname: Tienari
authors.forename: Tohru
authors.initials: T
authors.lastname: Matsuura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.forename: Alexander
authors.initials: A
authors.lastname: Zimprich
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Melissa
authors.initials: M
authors.lastname: Hanson
authors.forename: Shamaila
authors.initials: S
authors.lastname: Waseem
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: Maria
authors.initials: M
authors.lastname: Anvret
authors.forename: Olof
authors.initials: O
authors.lastname: Sydow
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People
chemical_list: D018388:Codon, Terminator; D000426:Alcohol Dehydrogenase