title: Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimer's disease.
abstract: OBJECTIVE
  To examine the genetic association of CYP2D6 locus with Lewy body variant (LBV) and Parkinson's disease (PD).
  
  
  METHODS
  Allelic association was studied in patients with pure AD, LBV, and PD by using the CYP2D microsatellite, the (dG-dT)n dinucleotide repeat (n=16 to 27) located between CYP2D8P and CYP2D7 genes, and the CYP2D6 B and D mutations.
  
  
  RESULTS
  We found overrepresentation of the alleles longer than 21 repeat (the long-type alleles) in LBV (allele frequency, 0.313) (odds ratio=1.99, p=0.019 by chi2 test) and in PD (0.298) (odds ratio=1.86, p=0.037), but not in pure AD (0.196), compared with the age-matched control (0.186). Strong association was noted of the long-type alleles with the CYP2D6 B mutation (odds ratio=88.50, p < 0.001 by Fisher's exact test), but not with the D mutation or the deletion of CYP2D6 gene.
  
  
  CONCLUSIONS
  The CYP2D locus is closely associated with LBV and PD. The CYP2D6 B mutation may be involved in pathogenesis of LBV and PD in a dominant-negative manner, or in the linkage disequilibrium of the CYP2D microsatellite to another pathogenic gene locus.
authors.affiliation: Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: D E
authors.initials: DE
authors.lastname: Kang
authors.forename: N
authors.initials: N
authors.lastname: Matoh
authors.forename: M
authors.initials: M
authors.lastname: Sundsmo
authors.forename: R G
authors.initials: RG
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Katzman
authors.forename: L J
authors.initials: LJ
authors.lastname: Thal
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: T
authors.initials: T
authors.lastname: Saitoh
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: E
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D019389:Cytochrome P-450 CYP2D6