ASSOCIATION OF CYP2D MICROSATELLITE POLYMORPHISM WITH LEWY BODY VARIANT OF ALZHEIMERS-DISEASE

Objective: To examine the genetic association of CYP2D6 locus with Lew y body variant (LBV) and Parkinson's disease (PD). Methods: Allelic as sociation was studied in patients with pure AD, LBV, and PD by using t he CYP2D microsatellite, the (dG-dT)n dinucleotide repeat (n = 16 to 2 7) located between CYP2D8P and CYP2D7 genes, and the CYP2D6 B and D mu tations. Results: We found overrepresentation of the alleles longer th an 21 repeat (the long-type alleles) in LBV (allele frequency, 0.313) (odds ratio = 1.99, p = 0.019 by chi(2) test) and in PD (0.298) (odds ratio = 1.86, p = 0.037), but not in pure AD (0.196), compared with th e age-matched control (0.186). Strong association was noted of the lon g-type alleles with the CYP2D6 B mutation (odds ratio = 88.50, p < 0.0 01 by Fisher's exact test), but not with the D mutation or the deletio n of CYP2D6 gene. Conclusions: The CYP2D locus is closely associated w ith 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 disequi librium of the CYP2D microsatellite to another pathogenic gene locus.