CYP2D Microsatellite Polymorphism in Lewy Body Variant of Alzheimer's Disease and Parkinson's Disease (BIOORGANIC CHEMISTRY-Molecular Clinical Chemistry)

Abstract

The Lewy body variant (LBV) has been recognized as a distinct subset of Alzheimer's disease (AD). In this study, we conducted an allelic association study in patients with pure AD, LBV and also Parkinson's disease (PD) by using the CYP2D microsatellite, the (dG-dT)n dinucleotide repeat (n = 16 - 27) located between CYP2D8P and CYP2D7 genes. The alleles longer than 21 repeat (the long-type alleles) were excessively represented in LBV (allele frequency, 0.313) compared with the age-matched control (0.186) (odds ratio = 1.99, p = 0.019 by c2 test). This overrepresentation was also found in PD (0.298) (odds ratio = 1.86, p = 0.037), but not in pure AD (0.196). The long-type alleles showed a strong association 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. These findings confirmed a close association of the CYP2D locus with LBV and PD, indicating the following two possibilities: the involvement of the CYP2D6 B mutation in pathogenesis of LBV and PD in a dominant-negative manner; or the linkage disequilibrium of the CYP2D microsatellite to another pathogenic gene locus. The microsatellite of the CYP2D locus could be an informative marker in the genetic study of LBV as well as PD.