The PSP-associated MAPT H1 subhaplotype in Guadeloupean atypical Parkinsonism

Authors

  • Agnès Camuzat BS,

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, UMR_S 679, Paris, France
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  • Marc Romana PhD,

    1. INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe
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  • Alexandra Dürr MD, PhD,

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, UMR_S 679, Paris, France
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  • Josué Feingold MD,

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, UMR_S 679, Paris, France
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  • Alexis Brice MD,

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, UMR_S 679, Paris, France
    3. UPMC Univ Paris 06, Pitié-Salpêtrière Medical School, Paris, France
    4. Département de Génétique et Cytogénétique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
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  • Merle Ruberg PhD,

    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, UMR_S 679, Paris, France
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  • Annie Lannuzel MD, PhD

    Corresponding author
    1. INSERM, UMR_S 679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 06, UMR_S 679, Paris, France
    3. Department of Neurology, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe
    • INSERM U679, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, Paris 75013, France; Department of Neurology, Centre Hospitalier Universitaire, Boite Postale 465, Pointe-à-Pitre 97159 Cedex
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  • Potential conflict of interest: None reported.

Abstract

The aim of this study was to determine whether the H1 subhaplotype in MAPT associated with progressive supranuclear palsy (PSP) in Caucasians confers risk for PSP-like atypical parkinsonism in Guadeloupe, a tauopathy. Guadeloupean controls and patients with atypical and idiopathic parkinsonism and ethnically and age-matched controls were genotyped for H1 and H2 alleles, then for the H1 subhaplotype associated with PSP in Caucasians, using previously described haplotype-tagging single nucleotide polymorphisms (Ht-SNPs) in linkage disequilibrium at the MAPT locus. Most Guadeloupean controls and patients were homozygous for the H1 allele; only 5% were heterozygous for the H2 allele, consistent with the European contribution to the racial admixture in Guadeloupe, but equivalent to the frequency found in Caucasian PSP patients. The frequencies of the Ht-SNPs used to determine the PSP-associated H1 subhaplotype in both Guadeloupean controls and parkinsonians were similar, indicating that the H1 subhaplotype associated with PSP in Caucasians was not a risk factor for PSP-like atypical parkinsonism in Guadeloupe. Interestingly, they were also similar to the frequencies in Caucasian PSP patients. The major H1 subhaplotype in Guadeloupe, determined by analysis of linkage desequibrium, differed from the major Caucasian subhaplotype, but corresponded to minor alleles previously described. © 2008 Movement Disorder Society

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