Tanaka S, Chen X, Xia Y, Kang D E, Matoh N, Sundsmo M, Thomas R G, Katzman R, Thal L J, Trojanowski J Q, Saitoh T, Ueda K, Masliah E
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624, USA.
Neurology. 1998 Jun;50(6):1556-62. doi: 10.1212/wnl.50.6.1556.
To examine the genetic association of CYP2D6 locus with Lewy body variant (LBV) and Parkinson's disease (PD).
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.
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.
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.
