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Further evidence for an association of the Paraoxonase 1 (PON1) Met-54 allele with Parkinson's disease

Authors

  • Andrea Carmine MSc,

    1. Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, Stockholm, Sweden
    2. Department of Clinical Genetics, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
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  • Silvia Buervenich BM,

    1. Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, Stockholm, Sweden
    2. Department of Clinical Genetics, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
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  • Olof Sydow MD, PhD,

    1. Department of Clinical Neuroscience, Neurology Section, Karolinska Hospital, Stockholm, Sweden
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  • Maria Anvret PhD,

    1. Department of Clinical Neuroscience, Neurology Section, Karolinska Hospital, Stockholm, Sweden
    2. AstraZeneca R&D Södertälje, Sweden
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  • Lars Olson PhD

    Corresponding author
    1. Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, Stockholm, Sweden
    • Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden
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Abstract

Paraoxonase1 (PON1) is an arylesterase mainly expressed in the liver that hydrolyzes organophosphates such as pesticides, reported risk factors for Parkinson's disease (PD), and other neurotoxins. A Leu-Met 54 polymorphism in the gene for PON1-affecting enzyme activity was recently shown, employing a new restriction enzyme technique, to be associated with Parkinson's disease. We examined the same polymorphism by automated capillary sequencing in a sample of Caucasian subjects from the Stockholm area in Sweden (127 healthy individuals and 114 patients with PD) and found similar distributions and a similar difference in our sample. The genotype distribution in our PD material was LL 36.0%, LM 45.6%, and MM 18.4%; in our control material, it was LL 45.7%, LM 44.1%, and MM 10.2%. Based on the previously established increase in allele frequencies of the lower-activity Met-variant of PON1, we could confirm a significant association using a one-sided χ2 test. Results remained significant with a two-sided χ2 test, allowing for both increases and decreases in frequencies. Our data confirm an association between the PON1 Leu-Met 54 polymorphism and PD by demonstrating a similar association. The distribution between familial and nonfamilial PD patients was equal. No other synonymous or nonsynonymous polymorphisms were found in the sequenced coding region of PON1. © 2002 Movement Disorder Society

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