Neurology, Vol 50, Issue 6 1556-1562, Copyright © 1998 by American Academy of Neurology

ARTICLES

Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimer's disease

S Tanaka, X Chen, Y Xia, DE Kang, N Matoh, M Sundsmo, RG Thomas, R Katzman, LJ Thal, JQ Trojanowski, T Saitoh, K Ueda and E Masliah
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624, USA.

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.

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