Association of Tau Haplotype-Tagging Polymorphisms with Parkinson’s Disease in Diverse Ethnic Parkinson’s Disease CohortsFung H.C.b-d · Xiromerisiou G.a, e · Gibbs J.R.a · Wu Y.R.d · Eerola J.f · Gourbali V.e · Hellström O.f · Chen C.M.d · Duckworth J.a · Papadimitriou A.e · Tienari P.J.g · Hadjigeorgiou G.M.e · Hardy J.b · Singleton A.B.a
aMolecular Genetics Unit, bLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Md., USA; cReta Lila Weston Institute of Neurological Studies, University College London, London, UK; dDepartment of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, Taiwan; eNeurogenetics Unit, Department of Neurology, Medical School, University of Thessaly, Larissa, Greece; fDepartment of Neurology, Seinäjoki Central Hospital, Seinäjoki, and gDepartment of Neurology, Helsinki University Central Hospital and University of Helsinki, Biomedicum-Helsinki, Neuroscience Programme, Helsinki, Finland
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Article / Publication Details
Background: The overlap in the clinical and pathological features of tauopathies and synucleinopathies raises the possibility that the tau protein may be important in Parkinson’s disease (PD) pathogenesis. Several MAPT polymorphisms that define the tau H1 haplotype have been investigated for an association with PD with conflicting results; however, two meta-analyses support an association between haplotype H1 and PD. Methods: In this study, we recruited 508 patients and 611 healthy controls from Greek, Finnish and Taiwanese populations. We examined the possible genetic role of variation within MAPT in PD using haplotype-tagging single polymorphisms (SNPs) in these ethnically different PD populations. Results: We identified a moderate association at SNP rs3785883 in the Greek cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively) as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p = 0.04 allelic) in the Finnish population. There were no significant differences in genotype or allele distribution between cases and controls in the Taiwanese cohort. Conclusion: We failed to demonstrate a consistent association between the MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically diverse populations. However, the data presented here suggest that subhaplotypes of haplotype H1 may confer susceptibility to PD, and that either allelic heterogeneity or different haplotype composition explain the divergent haplotype results.
© 2006 S. Karger AG, Basel
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